Datasets:
Dataset Viewer
pmid
int64 7.11M
40.4M
| title
stringlengths 1
553
| abstract
stringlengths 200
10.9k
| journal
stringlengths 3
239
| pub_year
int64 1.98k
2.02k
| pub_month
int64 1
12
| citation_count_within_one_year
int64 0
281
| citation_count_within_five_years
int64 0
1.17k
|
|---|---|---|---|---|---|---|---|
31,015,544 |
A novel wireless brain stimulation device for long-term use in freely moving mice.
|
Deep brain stimulation (DBS) has been used in clinical settings for many years despite a paucity of knowledge related to the anatomical and functional substrates that lead to benefits and/or side-effects in various disease contexts. In order to maximize the potential of this approach in humans, a better understanding of its mechanisms of action is absolutely necessary. However, the existing micro-stimulators available for pre-clinical models, are limited by the lack of relevant small size devices. This absence prevents sustained chronic stimulation and real time monitoring of animals during stimulation, parameters that are critical for comparison to clinical findings. We therefore sought to develop and refine a novel small wireless micro-stimulator as a means by which to study consequent behavioural to molecular changes in experimental animals. Building on previous work from our group, we refined our implantable micro-stimulator prototype, to be easily combined with intravital 2-photon imaging. Using our prototype we were able to replicate the well described clinical benefits on motor impairment in a mouse model of Parkinson's disease in addition to capturing microglia dynamics live during stimulation. We believe this new device represents a useful tool for performing pre-clinical studies as well as dissecting brain circuitry and function.
|
Scientific reports
| 2,019 | 4 | 0 | 8 |
27,153,125 |
Ecological momentary interventions in psychiatry.
|
In this review, we discuss feasibility, content, and where possible efficacy of ecological momentary interventions (EMIs) in psychiatry. EMIs adopt mobile devices, such as personal digital assistants or smartphones, for the delivery of treatments in the daily life of patients. We will discuss EMIs in the field of schizophrenia, bipolar disorder and major depression disorder, as well as one generic, transdiagnostic EMI.
|
Current opinion in psychiatry
| 2,016 | 7 | 2 | 75 |
23,748,408 |
Measuring motor coordination in mice.
|
Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance(2). Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available. The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test(12) or the Catwalk (Noldus)(15) apparatus are generally used to assess motor coordination in rats.
|
Journal of visualized experiments : JoVE
| 2,013 | 5 | 1 | 46 |
28,988,523 |
Immunopathology in drug resistant mesial temporal lobe epilepsy with different types of hippocampal sclerosis.
|
There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types.
|
The International journal of neuroscience
| 2,018 | 5 | 2 | 15 |
22,780,914 |
Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders.
|
6-[(3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic site. The physicochemical properties of the series were optimized to provide excellent in vitro and in vivo pharmacokinetics properties in multiple species including humans. It has been reported to elevate central cGMP levels in the brain and CSF of rodents. In addition, it exhibits procognitive activity in several rodent models and synaptic stabilization in an amyloid precursor protein (APP) transgenic mouse model. Recent disclosures from clinical trials confirm that it is well tolerated in humans and elevates cGMP in cerebral spinal fluid of healthy volunteers, confirming that it is a quality pharmacological tool for testing clinical hypotheses in disease states associated with impairment of cGMP signaling or cognition.
|
Journal of medicinal chemistry
| 2,012 | 11 | 4 | 33 |
24,736,169 |
Neonatal EEG at scalp is focal and implies high skull conductivity in realistic neonatal head models.
|
The potential improvements in spatial resolution of neonatal EEG used in source localization have been challenged by the insufficiencies in realistic neonatal head models. Our present study aimed at using empirical methods to indirectly estimate skull conductivity; the model parameter that is known to significantly affect the behavior of newborn scalp EEG and cause it to be markedly different from that of an adult. To this end, we used 64 channel EEG recordings to study the spatial specificity of scalp EEG by assessing the spatial decays in focal transients using both amplitudes and between-c'hannels linear correlations. The findings showed that these amplitudes and correlations decay within few centimeters from the reference channel/electrode, and that the nature of the decay is independent of the scalp area. This decay in newborn infants was found to be approximately three times faster than the corresponding decay in adult EEG analyzed from a set of 256 channel recordings. We then generated realistic head models using both finite and boundary element methods along with a manually segmented magnetic resonance images to study the spatial decays of scalp potentials produced by single dipole in the cortex. By comparing the spatial decays due to real and simulated EEG for different skull conductivities (from 0.003 to 0.3S/m), we showed that a close match between the empirical and simulated decays was obtained when the selected skull conductivity for newborn was around 0.06-0.2S/m. This is over an order of magnitude higher than the currently used values in adult head modeling. The results also showed that the neonatal scalp EEG is less smeared than that of an adult and this characteristic is the same across the entire scalp, including the fontanel region. These results indicate that a focal cortical activity is generally only registered by electrodes within few centimeters from the source. Hence, the conventional 10 to 20 channel neonatal EEG acquisition systems give a significantly spatially under sampled scalp EEG and may, consequently, give distorted pictures of focal brain activities. Such spatial specificity can only be reconciled by appreciating the anatomy of the neonatal head, especially the still unossified skull structure that needs to be modeled with higher conductivities than conventionally used in the adults.
|
NeuroImage
| 2,014 | 8 | 0 | 26 |
32,353,951 |
The Length and Number of Sedentary Bouts Predict Fibrinogen Levels in Postmenopausal Women.
|
Menopause is associated with adverse changes in coagulation homeostasis. We aimed to investigate the association between objectively measured sedentary behavior (SB) and SB bouts (i.e., number and length of SB bouts) vs. fibrinogen levels in post-menopausal women. Fifty-three post-menopausal women (age 59.8 ± 6.2 years, BMI 27.3 ± 4.4) wore a multisensory device (Sensewear Mini Armband, BodyMedia, Inc., Pittsburgh, PA) for 5 days, to measure SB and physical activity (PA). Blood samples were collected to measure serum fibrinogen. Fibrinogen was directly correlated with SB (r = -0.48,
|
International journal of environmental research and public health
| 2,020 | 4 | 3 | 12 |
26,214,729 |
N-Lipidated Peptide Dimers: Effective Antibacterial Agents against Gram-Negative Pathogens through Lipopolysaccharide Permeabilization.
|
Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were nonhemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.
|
Journal of medicinal chemistry
| 2,015 | 8 | 3 | 21 |
23,026,743 |
Neural dynamics and circuit mechanisms of decision-making.
|
In this review, I briefly summarize current neurobiological studies of decision-making that bear on two general themes. The first focuses on the nature of neural representation and dynamics in a decision circuit. Experimental and computational results suggest that ramping-to-threshold in the temporal domain and trajectory of population activity in the state space represent a duality of perspectives on a decision process. Moreover, a decision circuit can display several different dynamical regimes, such as the ramping mode and the jumping mode with distinct defining properties. The second is concerned with the relationship between biologically-based mechanistic models and normative-type models. A fruitful interplay between experiments and these models at different levels of abstraction have enabled investigators to pose increasingly refined questions and gain new insights into the neural basis of decision-making. In particular, recent work on multi-alternative decisions suggests that deviations from rational models of choice behavior can be explained by established neural mechanisms.
|
Current opinion in neurobiology
| 2,012 | 12 | 2 | 53 |
26,459,495 |
Occurrence of sickness absence and disability pension in relation to childbirth: A 16-year follow-up study of 6323 Swedish twins.
|
Pregnancy, delivery, and the postpartum period may imply morbidity leading to work incapacity; however, this is seldom studied. This study aimed to compare twin sisters giving or not giving birth regarding occurrence of sickness absence (SA) and disability pension (DP).
|
Scandinavian journal of public health
| 2,016 | 2 | 0 | 6 |
21,876,530 |
Lateral fluid percussion: model of traumatic brain injury in mice.
|
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.
|
Journal of visualized experiments : JoVE
| 2,011 | 8 | 0 | 21 |
30,308,256 |
Recent progress of drug nanoformulations targeting to brain.
|
Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.
|
Journal of controlled release : official journal of the Controlled Release Society
| 2,018 | 12 | 14 | 119 |
30,174,118 |
Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior.
|
Astrocytes tile the central nervous system, but their functions in neural microcircuits in vivo and their roles in mammalian behavior remain incompletely defined. We used two-photon laser scanning microscopy, electrophysiology, MINIscopes, RNA-seq, and a genetic approach to explore the effects of reduced striatal astrocyte Ca
|
Neuron
| 2,018 | 9 | 18 | 206 |
32,710,334 |
Effects of emotional maltreatment on semantic network activity during cognitive reappraisal.
|
Maltreatment experiences alter brain development associated with emotion processing, and dysregulation of emotion may trigger mental health problems in maltreated people. However, studies revealing alterations in brain networks during cognitive reappraisal in victims of maltreatment are strikingly insufficient. In this study, 27 healthy subjects were recruited. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Cognitive Emotion Regulation Questionnaire (CERQ), respectively. A cognitive reappraisal task using the International Affective Picture System (IAPS) was designed for functional magnetic resonance imaging (fMRI) experiments. Cognitive reappraisal induced more activities in the bilateral inferior parietal lobes and bilateral middle temporal gyri compared to the condition of "look" (false discovery rate (FDR) corrected p < 0.05). Furthermore, the left inferior parietal lobe and right middle temporal gyrus functionally interacted with components of the default mode network, including the precuneus and the posterior cingulate cortex. In residual analyses after controlling for age and depressive symptoms, the bilateral inferior parietal and middle temporal activities exhibited positive correlations with cognitive reappraisal abilities (all ps < 0.05), and emotional maltreatment experiences were negatively correlated with the left inferior parietal cortex, bilateral middle temporal cortex activities, and left inferior parietal lobe-posterior cingulate cortex connectivity (all ps < 0.05). We found that semantic networks were significant to cognitive reappraisal, especially reinterpretation, and negative effects of emotional maltreatment experiences on semantic network activities.
|
Brain imaging and behavior
| 2,021 | 6 | 2 | 9 |
27,137,838 |
Reciprocal interactions between circadian clocks and aging.
|
Virtually, all biological processes in the body are modulated by an internal circadian clock which optimizes physiological and behavioral performance according to the changing demands of the external 24-h world. This circadian clock undergoes a number of age-related changes, at both the physiological and molecular levels. While these changes have been considered to be part of the normal aging process, there is increasing evidence that disruptions to the circadian system can substantially impact upon aging and these impacts will have clear health implications. Here we review the current data of how both the physiological and core molecular clocks change with age and how feedback from external cues may modulate the aging of the circadian system.
|
Mammalian genome : official journal of the International Mammalian Genome Society
| 2,016 | 8 | 8 | 47 |
32,589,613 |
Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.
|
More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.
|
Aging
| 2,020 | 6 | 2 | 34 |
26,219,430 |
Alcohol dependence and treatment utilization in Europe - a representative cross-sectional study in primary care.
|
Alcohol dependence (AD) in Europe is prevalent and causes considerable health burden. Recognition by general practitioners (GPs) and provision of or referral to treatment may contribute to reduce this burden. This paper studied AD prevalence in varying European primary care settings and examined who received treatment.
|
BMC family practice
| 2,015 | 7 | 6 | 48 |
28,807,787 |
Trigeminal nerve stimulation induces Fos immunoreactivity in selected brain regions, increases hippocampal cell proliferation and reduces seizure severity in rats.
|
Sites and mechanisms by which trigeminal nerve stimulation (TNS) exerts beneficial effects on symptoms of drug-resistant epilepsy and depression are still unknown. Effects of short-term TNS on brain regions involved in the physiopathology of these disorders were investigated in this study. Forty male rats were assigned to three groups: TNS (undergoing electrical stimulation of the left infraorbitary nerve via surgically implanted cuff electrodes); Sham (undergoing surgical procedure but without a stimulation); Naïve rats. The effects of TNS (3-hour session; 30-s ON, 5-min OFF; 30Hz; 500μs; 2mA) were evaluated on: (i) behavioral pattern of pentylenetetrazole (PTZ)-induced seizures as measured by the Racine scale; (ii) c-Fos-like immunoreactivity in discrete brain areas; (iii) hippocampal cell proliferation by bromodeoxyuridine (BrdU)-like immunoreactivity. In comparison with Sham groups, TNS significantly decreased the duration of PTZ-induced seizures (p<0.05) and promoted a faster recovery (p<0.001) by reducing the most severe seizure types. In the TNS group the number of c-Fos-labeled cells was significantly increased (p<0.001) in the trigeminal nuclear complex, nucleus of the solitary tract, locus coeruleus, dorsal raphe nucleus, hippocampus, amygdala, endopiriform nucleus, entorhinal cortex and sensorimotor cortex. In the TNS group the number of BrdU-positive cells in the dentate gyrus was significantly greater with respect to both Naïve and Sham groups. Data show that acute TNS effectively counteracted PTZ-induced seizures and boosted hippocampal cell proliferation in rats. TNS increased c-Fos-like immunoreactivity in brainstem and forebrain structures which play a pivotal role in the physiopathology of epilepsy and depression.
|
Neuroscience
| 2,017 | 10 | 3 | 20 |
26,920,756 |
σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.
|
The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling.
|
Genetics
| 2,016 | 5 | 2 | 7 |
26,251,434 |
Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers.
|
The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method.
|
AJNR. American journal of neuroradiology
| 2,015 | 10 | 1 | 10 |
22,287,383 |
The need for complex ideas in anorexia nervosa: why biology, environment, and psyche all matter, why therapists make mistakes, and why clinical benchmarks are needed for managing weight correction.
|
Anorexia nervosa remains an enigma and its clinical challenge is intimidating. But the potential for new insights has been advancing, largely as a result of elegant research in the neurosciences that has modeled behavioral processes resembling key features of the illness. Unfortunately, many in the eating disorder field seem to know little of this work or the implication it holds for treatment philosophy. Instead, the knowledge void has been taken up recently by a host of misguided notions about etiology, blatantly dismissive attitudes toward psychological concepts, and ill-conceived beliefs about therapy priorities. This article is a clinical perspective on these issues.
|
The International journal of eating disorders
| 2,012 | 3 | 4 | 41 |
23,303,955 |
The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1).
|
The Neural cell adhesion molecule (NCAM) plays an important role in regulation of nervous system development. To expand our understanding of the molecular mechanisms via which NCAM influences differentiation of neurons, we used a yeast two-hybrid screening to search for new binding partners of NCAM and identified p21-activated kinase 1 (Pak1). We show that NCAM interacts with Pak1 in growth cones of neurons. The autophosphorylation and activity of Pak1 were enhanced when isolated growth cones were incubated with NCAM function triggering antibodies, which mimic the interaction between NCAM and its extracellular ligands. The association of Pak1 with cell membranes, the efficiency of Pak1 binding to its activators, and Pak1 activity were inhibited in brains of NCAM-deficient mice. NCAM-dependent Pak1 activation was abolished after lipid raft disruption, suggesting that NCAM promotes Pak1 activation in the lipid raft environment. Phosphorylation of the downstream Pak1 effectors LIMK1 and cofilin was reduced in growth cones from NCAM-deficient neurons, which was accompanied by decreased levels of filamentous actin and inhibited filopodium mobility in the growth cones. Dominant-negative Pak1 inhibited and constitutively active Pak1 enhanced the ability of neurons to increase neurite outgrowth in response to the extracellular ligands of NCAM. Our combined observations thus indicate that NCAM activates Pak1 to drive actin polymerization to promote neuronal differentiation.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,013 | 1 | 2 | 20 |
25,845,030 |
Solvent accessible surface area-based hot-spot detection methods for protein-protein and protein-nucleic acid interfaces.
|
Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to predict HS for protein-protein and protein-nucleic acid interactions with better statistics compared with the ones currently reported in literature. These models are based on solvent accessible surface area (SASA) and genetic conservation features subjected to simple Bayes networks (protein-protein systems) and a more complex multi-objective genetic algorithm-support vector machine algorithms (protein-nucleic acid systems). The best models for these interactions have been implemented in two free Web tools.
|
Journal of chemical information and modeling
| 2,015 | 5 | 3 | 15 |
26,429,678 |
Psychiatric classification - a developmental perspective.
|
Current classification systems treat developmental and adult psychopathologies as separate. However, as risk factors for psychiatric disorders are identified it is increasingly clear that these can lead to multiple outcomes across different developmental stages. Research and classification schemes will therefore in the future need to adopt a lifespan approach to risk.
|
The British journal of psychiatry : the journal of mental science
| 2,015 | 10 | 0 | 7 |
28,532,381 |
Visuomotor Functions in the Frontal Lobe.
|
This review surveys how vision becomes action through the frontal lobe. Signals from extrastriate areas create maps in frontal areas. These maps are shaped by visual features and shaded by goals, values, and experience, and they guide contingent activation of motor circuits to execute coordinated gaze, head, and limb movements. Frontal circuits also support the visual perception of learned objects, events, and actions. Other frontal circuits monitor consequences and exert executive control to improve the effectiveness of visually guided behavior.
|
Annual review of vision science
| 2,015 | 11 | 4 | 43 |
30,916,810 |
Neuroepigenetics of arousal: Gamma oscillations in the pedunculopontine nucleus.
|
Four major discoveries on the function of the pedunculopontine nucleus (PPN) have significantly advanced our understanding of the role of arousal in neurodegenerative disorders. The first was the finding that stimulation of the PPN-induced controlled locomotion on a treadmill in decerebrate animals, the second was the revelation of electrical coupling in the PPN and other arousal and sleep-wake control regions, the third was the determination of intrinsic gamma band oscillations in PPN neurons, and the last was the discovery of gene transcription resulting from the manifestation of gamma activity in the PPN. These discoveries have led to novel therapies such as PPN deep brain stimulation (DBS) for Parkinson's disease (PD), identified the mechanism of action of the stimulant modafinil, determined the presence of separate mechanisms underlying gamma activity during waking versus REM sleep, and revealed the presence of gene transcription during the manifestation of gamma band oscillations. These discoveries set the stage for additional major advances in the treatment of a number of disorders.
|
Journal of neuroscience research
| 2,019 | 12 | 1 | 4 |
33,349,698 |
An open letter to past, current and future mentors of Black neuroscientists.
|
We as Black trainees in neuroscience and co-founders of Black In Neuro wrote this open letter to thank the phenomenal mentors who came before us. We also aim to encourage and give advice to future mentors on how to effectively mentor the next generation of Black researchers.
|
Nature reviews. Neuroscience
| 2,021 | 2 | 5 | 12 |
25,980,363 |
ato-Gal4 fly lines for gene function analysis: Eya is required in late progenitors for eye morphogenesis.
|
The Gal4/UAS system is one of the most powerful tools for the study of cellular and developmental processes in Drosophila. Gal4 drivers can be used to induce targeted expression of dominant-negative and dominant-active proteins, histological markers, activity sensors, gene-specific dsRNAs, modulators of cell survival or proliferation, and other reagents. Here, we describe novel atonal-Gal4 lines that contain regions of the regulatory DNA of atonal, the proneural gene for photoreceptors, stretch receptors, auditory organ, and some olfactory sensilla. During neurogenesis, the atonal gene is expressed at a critical juncture, a time of transition from progenitor cell to developing neuron. Thus, these lines are particularly well suited for the study of the transcription factors and signaling molecules orchestrating this critical transition. To demonstrate their usefulness, we focus on two visual organs, the eye and the Bolwig. We demonstrate the induction of predicted eye phenotypes when expressing the dominant-negative EGF receptor or a dsRNA against Notch in the developing eye disc. In another example, we show the deletion of the Bolwig's organ using the proapoptotic factor Hid. Finally, we investigate the function of the eye specification factor Eyes absent or Eya in late retinal progenitors, shortly before they begin morphogenesis. We show that Eya is still required in these late progenitors to promote eye formation, and show failure to induce the target gene atonal and consequent lack of neuron formation.
|
Genesis (New York, N.Y. : 2000)
| 2,015 | 6 | 0 | 2 |
22,745,490 |
Loss of intranetwork and internetwork resting state functional connections with Alzheimer's disease progression.
|
Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain's functional organization.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,012 | 6 | 12 | 179 |
22,634,505 |
Theaflavin ameliorates behavioral deficits, biochemical indices and monoamine transporters expression against subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.
|
Evidence from clinical and experimental studies indicates that degeneration of nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). The present study was designed to investigate the neuroprotective potential of theaflavin (TF) on oxidative stress, monoamine transporters and behavioral abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration. TF, a black tea polyphenol, has been known to possess neuroprotective effects against ischemia, Alzheimer's disease and other neurodegenerative disorders, but the mechanisms underlying its beneficial effects on MPTP-induced dopaminergic neurodegeneration are poorly defined. Administration of MPTP (30 mg/kg bw for four consecutive days) led to increased oxidative stress and reduced behavior patterns (open field, rotarod and hang test), nigrostriatal dopamine transporter (DAT) (immunohistochemistry and Western blot) and vesicular monoamine transporter 2 (VMAT2) (Western blot) expressions. Pre-treatment with TF reduces oxidative stress, improves motor behavior and expression of DAT and VMAT2 in striatum and substantia nigra. These results indicate that TF might be beneficial in mitigating MPTP-induced damage of dopaminergic neurons, possibly via its neuroprotective and its antioxidant potential.
|
Neuroscience
| 2,012 | 8 | 3 | 22 |
29,966,850 |
Adverse effects of GHB-induced coma on long-term memory and related brain function.
|
Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced coma. Animal studies suggest that GHB induces oxidative stress in the hippocampus, resulting in memory impairments. However, the consequences of chronic GHB use and GHB-induced coma on human brain function and cognition are unknown.
|
Drug and alcohol dependence
| 2,018 | 9 | 3 | 16 |
23,815,670 |
The dimerization domain in outer segment guanylate cyclase is a Ca²⁺-sensitive control switch module.
|
Membrane-bound guanylate cyclases harbor a region called the dimerization or linker domain, which aids the enzymes in adopting an optimal monomer-monomer arrangement for catalysis. One subgroup of these guanylate cyclases is expressed in rod and cone cells of vertebrate retina, and mutations in the dimerization domain of rod outer segment guanylate cyclase 1 (ROS-GC1, encoded by the GUCY2D gene) correlate with retinal cone-rod dystrophies. We investigate how a Q847L/K848Q double mutation, which was found in patients suffering from cone-rod dystrophy, and the Q847L and K848Q single-point mutations affect the regulatory mechanism of ROS-GC1. Both the wild type and mutants of heterologously expressed ROS-GC1 were present in membranes. However, the mutations affected the catalytic properties of ROS-GC1 in different manners. All mutants had higher basal guanylate cyclase activities but lower levels of activation by Ca²⁺-sensing guanylate cyclase-activating proteins (GCAPs). Further, incubation with wild-type GCAP1 and GCAP2 revealed for all ROS-GC1 mutants a shift in Ca²⁺ sensitivity, but activation of the K848Q mutant by GCAPs was severely impaired. Apparent affinities for GCAP1 and GCAP2 were different for the double mutant and the wild type. Circular dichroism spectra of the dimerization domain showed that the wild type and mutants adopt a prevalently α-helical structure, but mutants exhibited lower thermal stability. Our results indicate that the dimerization domain serves as a Ca²⁺-sensitive control module. Although it is per se not a Ca²⁺-sensing unit, it seems to integrate and process information regarding Ca²⁺ sensing by sensor proteins and regulator effector affinity.
|
Biochemistry
| 2,013 | 7 | 1 | 16 |
27,172,792 |
Identifying and targeting determinants of melanoma cellular invasion.
|
Epithelial-to-mesenchymal transition is a critical process that increases the malignant potential of melanoma by facilitating invasion and dissemination of tumor cells. This study identified genes involved in the regulation of cellular invasion and evaluated whether they can be targeted to inhibit melanoma invasion. We identified Peroxidasin (PXDN), Netrin 4 (NTN4) and GLIS Family Zinc Finger 3 (GLIS3) genes consistently elevated in invasive mesenchymal-like melanoma cells. These genes and proteins were highly expressed in metastatic melanoma tumors, and gene silencing led to reduced melanoma invasion in vitro. Furthermore, migration of PXDN, NTN4 or GLIS3 siRNA transfected melanoma cells was inhibited following transplantation into the embryonic chicken neural tube compared to control siRNA transfected melanoma cells. Our study suggests that PXDN, NTN4 and GLIS3 play a functional role in promoting melanoma cellular invasion, and therapeutic approaches directed toward inhibiting the action of these proteins may reduce the incidence or progression of metastasis in melanoma patients.
|
Oncotarget
| 2,016 | 7 | 1 | 20 |
22,564,741 |
The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells.
|
Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.
|
Biochemical and biophysical research communications
| 2,012 | 7 | 4 | 10 |
24,948,399 |
Epigenetic regulation of persistent pain.
|
Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development or maintenance of persistent pain and possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain.
|
Translational research : the journal of laboratory and clinical medicine
| 2,015 | 1 | 6 | 40 |
26,505,566 |
Measuring macroscopic brain connections in vivo.
|
Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means.
|
Nature neuroscience
| 2,015 | 11 | 22 | 193 |
25,185,809 |
A functional circuit model of interaural time difference processing.
|
Inputs from the two sides of the brain interact to create maps of interaural time difference (ITD) in the nucleus laminaris of birds. How inputs from each side are matched with high temporal precision in ITD-sensitive circuits is unknown, given the differences in input path lengths from each side. To understand this problem in birds, we modeled the geometry of the input axons and their corresponding conduction velocities and latencies. Consistent with existing physiological data, we assumed a common latency up to the border of nucleus laminaris. We analyzed two biological implementations of the model, the single ITD map in chickens and the multiple maps of ITD in barn owls. For binaural inputs, since ipsi- and contralateral initial common latencies were very similar, we could restrict adaptive regulation of conduction velocity to within the nucleus. Other model applications include the simultaneous derivation of multiple conduction velocities from one set of measurements and the demonstration that contours with the same ITD cannot be parallel to the border of nucleus laminaris in the owl. Physiological tests of the predictions of the model demonstrate its validity and robustness. This model may have relevance not only for auditory processing but also for other computational tasks that require adaptive regulation of conduction velocity.
|
Journal of neurophysiology
| 2,014 | 12 | 5 | 10 |
26,853,734 |
Additive effect of BLA GABAA receptor mechanism and (+)-MK-801 on memory retention deficit, an isobologram analysis.
|
There is a near correlation between N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptors in the modulation of learning and memory in the basolateral amygdala (BLA). In this study, we investigated the involvement of GABAA receptors in the BLA in amnesia induced by (+)-MK-801, a noncompetitive antagonist of NMDA receptors, in male Wistar rats. After guide cannulae were bilaterally placed in the BLA, animals were trained in a step-through type passive avoidance task and then tested 24h after training to measure memory retrieval and locomotor activity. Post-training intra-BLA microinjection of (+)-MK-801 (0.5 μg/rat) and GABAA receptor agonists (muscimol at doses 0.05 and 0.1 μg/rat) or antagonist (bicuculline at doses 0.05 and 0.1 μg/rat) decreased step-through latency during retrieval but did not alter locomotor activity. Results also showed that a subthreshold dose of muscimol (0.025 μg/rat) potentiated impairment induced by (+)-MK-801, whereas bicuculline (0.025 μg/rat) restored it. Furthermore, the highest dose of muscimol (0.5 μg/rat) increased locomotor activity induced by (+)-MK-801. Isobologram analysis showed that there was an additive but not synergistic effect between muscimol and (+)-MK-801 on memory retention deficits in the BLA. In conclusion, muscimol and bicuculline decreased retention of memory formation in the BLA, and GABAA receptors in the BLA may be involved in the additive effect on (+)-MK-801-induced memory retention deficits.
|
Pharmacology, biochemistry, and behavior
| 2,016 | 4 | 0 | 4 |
28,801,917 |
Attention-Deficit/Hyperactivity Disorder (ADHD): Interaction between socioeconomic status and parental history of ADHD determines prevalence.
|
Many studies have reported a higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) among disadvantaged populations, but few have considered how parental history of ADHD might modify that relationship. We evaluated whether the prevalence of ADHD varies by socioeconomic status (SES) and parental history of ADHD in a population-sample of elementary school children age 6-14 years.
|
Journal of child psychology and psychiatry, and allied disciplines
| 2,018 | 3 | 3 | 37 |
29,373,439 |
Psychological Factors and Outcomes in the Surgical Treatment of Pediatric Patients With Median Arcuate Ligament Syndrome.
|
Median arcuate ligament syndrome (MALS) is a frequently overlooked cause of chronic abdominal pain (CAP), and results in many symptoms that mimic other gastrointestinal conditions that result in CAP. A small, but growing body of literature indicates that surgery improves quality of life (QOL) in patients with MALS. The purpose of the current study was to examine the psychological characteristics of pediatric patients with MALS to determine their prevalence and impact on surgical outcomes.
|
Journal of pediatric gastroenterology and nutrition
| 2,018 | 6 | 1 | 8 |
27,161,524 |
DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor.
|
Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.
|
Neuron
| 2,016 | 6 | 4 | 33 |
21,309,750 |
The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation.
|
The non-RTK (receptor tyrosine kinase) ACK1 [activated Cdc42 (cell division cycle 42)-associated kinase 1] binds a number of RTKs and is associated with their endocytosis and turnover. Its mode of activation is not well established, but models have suggested that this is an autoinhibited kinase. Point mutations in its SH3 (Src homology 3)- or EGF (epidermal growth factor)-binding domains have been reported to activate ACK1, but we find neither of the corresponding W424K or F820A mutations do so. Indeed, deletion of the various ACK1 domains C-terminal to the catalytic domain are not associated with increased activity. A previous report identified only one major tyrosine phosphorylated protein of 60 kDa co-purified with ACK1. In a screen for new SH3 partners for ACK1 we found multiple Src family kinases; of these c-Src itself binds best. The SH2 and SH3 domains of Src interact with ACK1 Tyr518 and residues 623-652 respectively. Src targets the ACK1 activation loop Tyr284, a poor autophosphorylation site. We propose that ACK1 fails to undergo significant autophosphorylation on Tyr284 in vivo because it is basophilic (whereas Src is acidophilic). Subsequent ACK1 activation downstream of receptors such as EGFR (EGF receptor) (and Src) promotes turnover of ACK1 in vivo, which is blocked by Src inhibitors, and is compromised in the Src-deficient SYF cell line. The results of the present study can explain why ACK1 is responsive to so many external stimuli including RTKs and integrin ligation, since Src kinases are commonly recruited by multiple receptor systems.
|
The Biochemical journal
| 2,011 | 4 | 0 | 11 |
20,637,543 |
Reversal of neuropathic pain by HSV-1-mediated decrease of noradrenaline in a pain facilitatory area of the brain.
|
Descending modulation of nociceptive transmission depends on the release of noradrenaline at the spinal cord. The role of noradrenaline in the control of nociceptive transmission at the supraspinal pain control system remains understudied. As chronic pain is associated with enhanced descending facilitation of nociceptive transmission, we sought to determine the role of noradrenaline in pain facilitation from the brain during neuropathic pain. We determined the action of the noradrenergic input to the dorsal reticular nucleus (DRt), a unique pain facilitatory area, using the spared nerve injury model. Injections of the α1-adrenoreceptor agonist phenylephrine into the DRt induced hyperalgesia and allodynia, indicating that α1-adrenoreceptors enhance the facilitatory action of the nucleus. This led us to reduce noradrenaline release at the DRt using a viral vector derived from the Herpes Simplex virus type 1 (HSV-1) which carried the tyrosine hydroxylase (TH) transgene in antisense orientation. The reduction of noradrenaline release, confirmed by microdialysis experiments, induced a long-lasting attenuation of pain responses, which was reverted by the local administration of phenylephrine. The present study indicates that the noradrenergic modulation of a pronociceptive area at the supraspinal pain control system accounts for pain facilitation, through the activation of α1-adrenoreceptors. The study also shows that sustained effects on chronic pain can be achieved by decreasing the release of noradrenaline in a pain facilitatory centre of the brain using gene transfer.
|
Pain
| 2,010 | 10 | 5 | 24 |
27,197,831 |
Sex-dependent mitochondrial respiratory impairment and oxidative stress in a rat model of neonatal hypoxic-ischemic encephalopathy.
|
Increased male susceptibility to long-term cognitive deficits is well described in clinical and experimental studies of neonatal hypoxic-ischemic encephalopathy. While cell death signaling pathways are known to be sexually dimorphic, a sex-dependent pathophysiological mechanism preceding the majority of secondary cell death has yet to be described. Mitochondrial dysfunction contributes to cell death following cerebral hypoxic-ischemia (HI). Several lines of evidence suggest that there are sex differences in the mitochondrial metabolism of adult mammals. Therefore, this study tested the hypothesis that brain mitochondrial respiratory impairment and associated oxidative stress is more severe in males than females following HI. Maximal brain mitochondrial respiration during oxidative phosphorylation was two-fold more impaired in males following HI. The endogenous antioxidant glutathione was 30% higher in the brain of sham females compared to males. Females also exhibited increased glutathione peroxidase (GPx) activity following HI injury. Conversely, males displayed a reduction in mitochondrial GPx4 protein levels and mitochondrial GPx activity. Moreover, a 3-4-fold increase in oxidative protein carbonylation was observed in the cortex, perirhinal cortex, and hippocampus of injured males, but not females. These data provide the first evidence for sex-dependent mitochondrial respiratory dysfunction and oxidative damage, which may contribute to the relative male susceptibility to adverse long-term outcomes following HI. Lower basal GSH levels, lower post-hypoxic mitochondrial glutathione peroxidase (mtGPx) activity, and mitochondrial glutathione peroxidase 4 (mtGPx4) protein levels may contribute to the susceptibility of the male brain to oxidative damage and mitochondrial dysfunction following neonatal hypoxic-ischemia (HI). Treatment of male pups with acetyl-L-carnitine (ALCAR) protects against the loss of mtGPx activity, mtGPx4 protein, and increases in protein carbonylation after HI. These findings provide novel insight into the pathophysiology of sexually dimorphic outcomes following HI.
|
Journal of neurochemistry
| 2,016 | 6 | 10 | 50 |
32,585,130 |
Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1.
|
An understanding of the structure-dynamics relationship is essential for understanding how a protein works. Prior research has shown that the activity of a protein correlates with intradomain dynamics occurring at picosecond to millisecond timescales. However, the correlation between interdomain dynamics and the function of a protein is poorly understood. Here, we show that communications between the catalytic and hemopexin domains of matrix metalloprotease-1 (MMP1) on type 1 collagen fibrils correlate with its activity. Using single-molecule Förster resonance energy transfer, we identified functionally relevant open conformations in which the two MMP1 domains are well separated, which were significantly absent for catalytically inactive point mutant (E219Q) of MMP1 and could be modulated by an inhibitor or an enhancer of activity. The observed relevance of open conformations resolves the debate about the roles of open and closed MMP1 structures in function. We fitted the histograms of single-molecule Förster resonance energy transfer values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We used a two-state Poisson process to describe the dynamics and calculate the kinetic rates from the fit parameters. All-atom and coarse-grained simulations reproduced some of the experimental features and revealed substrate-dependent MMP1 dynamics. Our results suggest that an interdomain separation facilitates opening up the catalytic pocket so that the collagen chains come closer to the MMP1 active site. Coordination of functional conformations at different parts of MMP1 occurs via allosteric communications that can take place via interactions mediated by collagen even if the linker between the domains is absent. Modeling dynamics as a Poisson process enables connecting the picosecond timescales of molecular dynamics simulations with the millisecond timescales of single-molecule measurements. Water-soluble MMP1 interacting with water-insoluble collagen fibrils poses challenges for biochemical studies that the single-molecule tracking can overcome for other insoluble substrates. Interdomain communications are likely important for multidomain proteins.
|
Biophysical journal
| 2,020 | 7 | 4 | 12 |
22,588,670 |
Secular changes in personality: study on 75-year-olds examined in 1976-1977 and 2005-2006.
|
In order to study secular changes in personality factors neuroticism and extroversion, representative population samples of non-demented 75-year-olds underwent psychiatric examinations in 1976-1977 (total n = 223, 138 women, 85 men) and 2005-2006 (total n = 556, 322 women and 234 men).
|
International journal of geriatric psychiatry
| 2,013 | 3 | 2 | 7 |
22,171,033 |
Active action potential propagation but not initiation in thalamic interneuron dendrites.
|
Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K-based action potentials can evoke calcium transients in dendrites via local active conductances, making the backpropagating action potential a candidate for dendritic neurotransmitter release. In this study, we used high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation rapidly and actively backpropagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid backpropagation into the dendritic arbor depended upon voltage-gated sodium and tetraethylammonium chloride-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then backpropagate with high fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,011 | 12 | 2 | 21 |
27,976,689 |
The proteomic profile of whole and glandular saliva in healthy pain-free subjects.
|
Determination of the variability in the salivary proteome is a prerequisite for the development of saliva as a diagnostic and prognostic tool in particular physiological states. In this context, it is important that technical variability induced by sample collection and processing is kept at minimum to be able to reproducibly assess variability in states of health and disease. In the current study, the proteome profile in unstimulated and stimulated whole, parotid and sublingual saliva was investigated using two-dimensional gel electrophoresis. Saliva samples were structurally collected from ten examined and characterized healthy individuals during the exactly same conditions. The results demonstrated that different collection methods provide clear differences in the snapshot of the salivary proteome and also in the relative amount of specific proteins. The variable nature of the salivary proteome suggests that different approaches may have to be adopted when studying its composition or its possible role as an indicator for particular physiological states. The results emphasize the importance of consistency when collecting saliva samples for proteomic analysis.
|
Scientific reports
| 2,016 | 12 | 2 | 42 |
25,700,195 |
Mentoring the next generation of neuroscience nurses: a pilot study of mentor engagement within an academic-service partnership.
|
Resulting from a system-wide launch of an academic-service partnership that united a research-intensive School of Nursing and a tertiary healthcare system, neuroscience nurses used a team-based approach in mentoring undergraduate nursing students in neuroscience nursing. They linked their team approach to the Institute of Medicine's Future of Nursing report and American Association of Neuroscience Nurses' (2012) strategic plan to prepare neuroscience nurses for the future. Using case reports containing both the mentors' and students' perspective, we showcase sophomore nursing students' development in neuroscience nursing with focus on their developing skills in competency, leadership, and collaboration. Results from this implementation phase include improved reliability in performing undergraduate neurological assessments; developing competency in collaborating with the health team using a culturally sensitive approach; beginning leadership in managing a patient with seizures; and collaborating with families in patient-family-focused care. Evaluation of the effectiveness of this mentored approach to clinical undergraduate nursing education will focus on confidence building for students and mentors.
|
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses
| 2,015 | 4 | 0 | 1 |
33,947,543 |
Radio-sensitivity enhancement in HT29 cells through magnetic hyperthermia in combination with targeted nano-carrier of 5-Flourouracil.
|
Normal tissue complication and development of radioresistance in cancer cells are known as the main challenges of ionizing radiation treatment. In the current study, we intended to induce selective radiosensitization in HT29 cancer cells by developing folic acid modified magnetic triblock copolymer nanoparticles as carrier of 5-Flourouracil (5-FU) which was further used in combination with hyperthermia. The aforementioned nanoparticles were synthesized and characterized by differential scanning calorimetric analysis (DSC), UV-visible spectroscopy, dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM). These nanoparticles were also assessed to determine drug loading capacity (DLC %) and drug release profile. The cytotoxicity of nanoparticles was evaluated on two different cell lines: HUVEC and HT29. Furthermore, radiosensitivity induction of the nanoparticles with and without exposure of alternative magnetic field was investigated. MTT-based cytotoxicity assay demonstrated that the therapeutic ratio was enhanced in response to using 5-FU-loaded nanoparticles as compared to 5-FU. Various characterizations including gene expression study, measurement of reactive oxygen species (ROS) generation, Annexin V/PI staining, and clonogenic assay revealed that ionizing radiation in combination with hyperthermia in the presence of the synthesized nanoparticles led to maximal anti-cancer effects as compared to other single (P < 0.001) and combined treatments (P < 0.01). Our results suggested that combined treatment based on using folic acid modified magnetic copolymer nanoparticle as carrier of 5-FU accompanied with hyperthermia could be proposed as an efficient approach to enhance radiation effects in cancer cells.
|
Materials science & engineering. C, Materials for biological applications
| 2,021 | 5 | 3 | 17 |
27,283,589 |
Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats.
|
Androgen loss is an important clinical concern because of its cognitive and behavioral effects. Changes in androgen levels are also suspected to contribute to neurological disease. However, the available data on the effects of androgen deprivation in areas of the brain that are central to cognition, like the hippocampus, are mixed. In this study, morphological analysis of pyramidal cells was used to investigate if structural changes could potentially contribute to the mixed cognitive effects that have been observed after androgen loss in males. Male Sprague-Dawley rats were orchidectomized or sham-operated. Two months later, their brains were Golgi-impregnated for morphological analysis. Morphological endpoints were studied in areas CA3 and CA1, with comparisons to females either intact or 2 months after ovariectomy. CA3 pyramidal neurons of orchidectomized rats exhibited marked increases in apical dendritic arborization. There were increases in mossy fiber afferent density in area CA3, as well as robust enhancements to dendritic structure in area CA3 of orchidectomized males, but not in CA1. Remarkably, apical dendritic length of CA3 pyramidal cells increased, while spine density declined. By contrast, in females overall dendritic structure was minimally affected by ovariectomy, while dendritic spine density was greatly reduced. Sex differences and subfield-specific effects of gonadal hormone deprivation on the hippocampal circuitry may help explain the different behavioral effects reported in males and females after gonadectomy, or other conditions associated with declining gonadal hormone secretion.
|
Brain structure & function
| 2,017 | 1 | 1 | 19 |
32,782,247 |
Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis.
|
The central role played by cerebrospinal-fluid (CSF) examinations including antineuronal autoantibody (Ab) testing is increasingly recognized in psychiatry. The rationale of this study was to present a multimodally investigated group of patients. In total, 992 patients were analyzed for CSF alterations: 456 patients with schizophreniform and 536 with affective syndromes. Ab measurement included testing for established antineuronal IgG-Abs against intracellular antigens in serum (Yo/Hu/Ri/cv2[CRMP5]/Ma1/Ma2/SOX1/TR[DNER]/Zic4/amphiphysin/GAD65) and for cell surface antigens in the CSF (NMDAR/AMPA-1/2-R/GABA-B-R/LGI1/CASPR2/DPPX). In 30 patients with "red flags" for autoimmune psychosis, "tissue tests" were performed. Additional diagnostics included MRI and EEG analyses. CSF white-blood-cell counts were increased in 4% and IgG indices in 2%; CSF-specific oligoclonal bands were detected in 4%; overall, 8% displayed signs of neuroinflammation. In addition, 18% revealed increased albumin quotients. Antineuronal Abs against intracellular antigens were detected in serum in 0.6%. Antineuronal Abs against established cell surface antigens were detected in serum of 1% and in the CSF of 0.3% (CSF samples were only questionably positive). Abnormal IgG binding in "tissue tests" was detected in serum of 23% and in CSF of 27%. In total, 92% of the Ab-positive patients demonstrated at least one sign of brain involvement in additional diagnostics using CSF, MRI, EEG, and FDG-PET. In summary, CSF basic analyses revealed signs of blood-brain-barrier dysfunction and neuroinflammation in relevant subgroups of patients. Established antineuronal IgG-Abs were rare in serum and even rarer in the CSF. "Tissue tests" revealed frequent occurrences of Ab-binding; therefore, novel antineuronal Abs could play a relevant role in psychiatry.
|
Translational psychiatry
| 2,020 | 8 | 11 | 63 |
26,162,240 |
Effects of acoustic trauma on the auditory system of the rat: The role of microglia.
|
Exposure to loud, prolonged sounds (acoustic trauma, AT) leads to the death of both inner and outer hair cells (IHCs and OHCs), death of neurons of the spiral ganglion and degeneration of the auditory nerve. The auditory nerve (8cn) projects to the three subdivisions of the cochlear nuclei (CN), the dorsal cochlear nucleus (DC) and the anterior (VCA) and posterior (VCP) subdivisions of the ventral cochlear nucleus (VCN). There is both anatomical and physiological evidence for plastic reorganization in the denervated CN after AT. Anatomical findings show axonal sprouting and synaptogenesis; physiologically there is an increase in spontaneous activity suggesting reorganization of circuitry. The mechanisms underlying this plasticity are not understood. Recent data suggest that activated microglia may have a role in facilitating plastic reorganization in addition to removing trauma-induced debris. In order to investigate the roles of activated microglia in the CN subsequent to AT we exposed animals to bilateral noise sufficient to cause massive hair cell death. We studied four groups of animals at different survival times: 30 days, 60 days, 6 months and 9 months. We used silver staining to examine the time course and pattern of auditory nerve degeneration, and immunohistochemistry to label activated microglia in the denervated CN. We found both degenerating auditory nerve fibers and activated microglia in the CN at 30 and 60 days and 6 months after AT. There was close geographic overlap between the degenerating fibers and activated microglia, consistent with a scavenger role for activated microglia. At the longest survival time, there were still silver-stained fibers but very little staining of activated microglia in overlapping regions. There were, however, activated microglia in the surrounding brainstem and cerebellar white matter.
|
Neuroscience
| 2,015 | 9 | 0 | 19 |
23,924,992 |
C-terminal alternative splicing of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity.
|
The transcripts of L-type voltage-gated calcium channels (CaV) 1.3 undergo extensive alternative splicing. Alternative splicing, particularly in the C terminus, drastically modifies gating properties of the channel. However, little is known about whether alternative splicing could modulate the pharmacologic properties of CaV1.3 in a manner similar to the paralogous CaV1.2. Here we undertook the screening of different channel splice isoforms harboring splice variations in either the IS6 segment or the C terminus. Unexpectedly, while inclusion of exon 8a or 8, which code for IS6, did not alter dihydropyridine (DHP) sensitivity, distinct pharmacologic properties were observed for the various C-terminal splice isoforms. In the presence of external Ca(2+), fast inactivating splice variants including CaV1.342a and CaV1.343s with intact calmodulin-IQ domain interaction showed consistently low DHP sensitivity. Interestingly, attenuation of calcium-dependent inactivation with overexpression of calmodulin34 did not enhance the sensitivity of CaV1.342a, suggesting that the low DHP sensitivity may not be a result of fast channel inactivation. Alternatively, disruption of calmodulin-IQ domain binding in the CaV1.3Δ41 and full-length CaV1.342 channels was associated with heightened DHP sensitivity. In distinct contrast to the well-known modulation of DHP blockade of CaV1.2 channels, this study has therefore uncovered a novel mechanism for modulation of the pharmacologic properties of CaV1.3 channels through posttranscriptional modification of the C terminus.
|
Molecular pharmacology
| 2,013 | 10 | 3 | 22 |
31,732,108 |
Mechanisms Underlying the Hyperexcitability of CA3 and Dentate Gyrus Hippocampal Neurons Derived From Patients With Bipolar Disorder.
|
Approximately 1 in every 50 to 100 people is affected with bipolar disorder (BD), making this disease a major economic burden. The introduction of induced pluripotent stem cell methodology enabled better modeling of this disorder.
|
Biological psychiatry
| 2,020 | 7 | 8 | 47 |
25,979,487 |
Neuropeptide S reduces mouse aggressiveness in the resident/intruder test through selective activation of the neuropeptide S receptor.
|
Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). In particular NPS evokes robust anxiolytic-like effects in rodents together with a stimulant and arousal promoting action. The aim of the study was to investigate the effects of NPS on the aggressiveness of mice subjected to the resident/intruder test. Moreover the putative role played by the endogenous NPS/NPSR system in regulating mice aggressiveness was investigating using mice lacking the NPSR receptor (NPSR(-/-)) and the NPSR selective antagonists [(t)Bu-D-Gly(5)]NPS and SHA 68. NPS (0.01-1 nmol, icv) reduced, in a dose dependent manner, both the time that resident mice spent attacking the intruder mice and their number of attacks, producing pharmacological effects similar to those elicited by the standard anti-aggressive drug valproate (300 mg/kg, ip). This NPS effect was evident in NPSR wild type (NPSR(+/+)) mice but completely disappeared in NPSR(-/-) mice. Moreover, NPSR(-/-) mice displayed a significantly higher time spent attacking than NPSR(+/+) mice. [(t)Bu-D-Gly(5)]NPS (10 nmol, icv) did not change the behavior of mice in the resident/intruder test but completely counteracted NPS effects. SHA 68 (50 mg/kg, ip) was inactive per se and against NPS. In conclusion, this study demonstrated that NPS produces anti-aggressive effects in mice through the selective activation of NPSR and that the endogenous NPS/NPSR system can exert a role in the control of aggressiveness levels under the present experimental conditions.
|
Neuropharmacology
| 2,015 | 10 | 1 | 11 |
26,469,048 |
Progress and challenges in probing the human brain.
|
Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience.
|
Nature
| 2,015 | 10 | 11 | 127 |
23,706,187 |
The central circadian timing system.
|
It has been known since the 1970s that the suprachiasmatic nucleus (SCN) is the brain's main biological clock, and since the 1990s that it uses a genetic clock based on transcriptional-translational loops to tell time. However, the recent demonstration that many other cells in the brain and the body also make use of the same genetic clock raises the question of how the SCN synchronizes all of the other clocks to arrive at a coherent circadian profile of physiology and behavior. In this review, we re-examine the evidence that the SCN clock is necessary for bringing order to the body's biological rhythms, and the circuitry of the circadian timing system by which it accomplishes this goal. Finally, we review the evidence that under conditions of restricted food availability, other clocks may be able to take over from the SCN to determine rhythms of behavior and physiology.
|
Current opinion in neurobiology
| 2,013 | 10 | 7 | 43 |
26,838,118 |
Concurrent Risperidone Administration Attenuates the Development of Locomotor Sensitization Following Sub-Chronic Phencyclidine in Rats.
|
In schizophrenia early treatment may prevent disorder onset, or at least minimize its impact, suggesting possible neuroprotective properties of antipsychotics. The present study investigates the effects of chronic treatment with the atypical antipsychotic, risperidone, on locomotor sensitization in the subchronic phencyclidine-treated rat.
|
Pharmacopsychiatry
| 2,016 | 3 | 0 | 1 |
26,272,028 |
A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis.
|
Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing-remitting (RR) and secondary progressive (SP) MS.
|
Journal of neurology, neurosurgery, and psychiatry
| 2,016 | 7 | 2 | 9 |
23,283,340 |
Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth.
|
Intracellular Ca(2+) signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca(2+) transients. Ca(2+) influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca(2+) influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,013 | 1 | 7 | 41 |
18,418,782 |
Severity of nicotine dependence moderates performance on perceptual-motor tests of attention.
|
Acute abstinence from cigarette smoking by nicotine-dependent smokers has been linked with cognitive deficits, but the role of nicotine dependence per se in these effects is not known. We therefore tested the relationships of nicotine dependence and smoking history with performance in perceptual-motor, timed tests of attention. Nicotine-dependent smokers (n = 37) and nonsmokers (n = 48), 18-55 years old, took both the d2 Test of Attention and the Digit Symbol Test on each of 2 test days. For smokers, testing on one day began after ad libitum smoking (<45 min since last cigarette); and on the other day, it began after overnight abstinence (>13 hr since last cigarette). On each test day, there were two test blocks with an intervening break, when only the smokers each smoked one cigarette. There were no significant effects of abstinence or of smoking one cigarette on the performance of smokers; however, across conditions, the smokers' performance on both tests correlated negatively with severity of nicotine dependence but not lifetime cigarette consumption or cigarette craving. Smokers with high nicotine dependence performed more slowly on both tests than less dependent smokers or nonsmokers. The findings suggest that severity of nicotine dependence and slowness in perceptual-motor tasks of attention share an underlying basis.
|
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
| 2,008 | 4 | 0 | 7 |
29,199,893 |
Nanoparticle/siRNA-based therapy strategies in glioma: which nanoparticles, which siRNAs?
|
Nanomedicines allow for the delivery of small interfering RNAs (siRNAs) that are otherwise barely suitable as therapeutics for inducing RNA interference (RNAi). In preclinical studies on siRNA-based glioma treatment in vivo, various groups of nanoparticle systems, routes of administration and target genes have been explored. Targeted delivery by functionalization of nanoparticles with a ligand for crossing the blood-brain barrier and/or for enhanced target cell transfection has been described as well. Focusing on nanoparticle developments in the last approximately 10 years, this review article gives a comprehensive overview of nanoparticle systems for siRNA delivery into glioma and of preclinical in vivo studies. Furthermore, it discusses various target genes and highlights promising strategies with regard to target gene selection and combination therapies.
|
Nanomedicine (London, England)
| 2,018 | 1 | 1 | 23 |
22,245,502 |
Naloxone in ultralow concentration restores endomorphin-1-evoked Ca²⁺ signaling in lipopolysaccharide pretreated astrocytes.
|
Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca²⁺ responses. EM-1 stimulated the μ-opioid receptor from 10⁻¹⁵ M up to 10⁻⁴ M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca²⁺ responses. However, a combination of ultralow concentration naloxone (10⁻¹² M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca²⁺ responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca²⁺ transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca²⁺ transients were oscillated. To restore the EM-1-evoked Ca²⁺ transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca²⁺ transients.
|
Neuroscience
| 2,012 | 3 | 0 | 13 |
28,820,427 |
A Review of the Neuropsychological Dimensions of Tourette Syndrome.
|
Neurocognitive functioning in Tourette syndrome (TS) has been the subject of intensive research in the past 30 years. A variety of impairments, presumably related to frontal and frontostriatal dysfunctions, have been observed. These impairments were found in various domains, such as attention, memory, executive functions, language, motor and visuomotor functions, among others. In line with contemporary research, other neurocognitive domains have recently been explored in TS, bringing evidence of altered social reasoning, for instance. Therefore, the aims of this review are to give an overview of the neuropsychological dimensions of TS, to report how neuropsychological functions evolve from childhood to adulthood, and to explain how various confounding factors can affect TS patients' performance in neuropsychological tasks. Finally, an important contribution of this review is to show how recent research has confirmed or changed our beliefs about neuropsychological functioning in TS.
|
Brain sciences
| 2,017 | 8 | 3 | 26 |
33,921,465 |
MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.
|
Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.
|
Brain sciences
| 2,021 | 4 | 0 | 3 |
19,229,522 |
The role of noradrenaline and 5-hydroxytryptamine in yohimbine-induced increases in alcohol-seeking in rats.
|
We previously showed that systemic administration of the prototypical alpha-2 noradrenaline (NA) receptor antagonist yohimbine increases alcohol self-administration and reinstatement. Yohimbine also acts as an agonist of 5-hydroxytryptamine (5-HT) 5-HT1A receptors, which have been shown to be involved in alcohol seeking. Here, we determined the contributions of the alpha-2 and 5-HT1A properties of yohimbine to its effects on alcohol seeking.
|
Psychopharmacology
| 2,009 | 6 | 5 | 30 |
24,965,042 |
Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease.
|
Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.
|
BMC neuroscience
| 2,014 | 6 | 2 | 9 |
31,202,956 |
French clinical guidelines for peripheral motor nerve blocks in a PRM setting.
|
Motor nerve blocks with anesthetic drug for local anesthesia are commonly used in physical and rehabilitation medicine (PRM), especially in the field of spasticity. Guidelines in this context are currently lacking.
|
Annals of physical and rehabilitation medicine
| 2,019 | 7 | 0 | 21 |
29,298,861 |
Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish.
|
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant (POP), an unintentional byproduct of various industrial processes, and a human carcinogen. The expression of the cytochrome P450 1A (cyp1a) gene is upregulated in the presence of TCDD through activating the aryl hydrocarbon receptor pathway in a dose-dependent manner. Several essential response elements, including the 8 potential xenobiotic response elements in the cyp1a promoter region, have been identified to be the main functional parts for the response to TCDD. Thus, we aimed to develop a convenient and sensitive biomonitoring tool to examine the level of POPs in the environment and evaluate its potential human health risks by TCDD. Here, we established a transgenic zebrafish model with a red fluorescent reporter gene ( mCherry) using the truncated cyp1a promoter. Under exposure to TCDD, the expression pattern of mCherry in the reporter zebrafish mirrored that of endogenous cyp1a mRNA, and the primary target tissues for TCDD were the brain vessels, liver, gut, cloaca, and skin. Our results indicated that exposure of the embryos to TCDD at concentrations as low as 0.005 nM for 48 h, which did not elicit morphologic abnormalities in the embryos, markedly increased mCherry expression. In addition, the reporter embryos responded to other POPs, and primary liver cell culture of zebrafish revealed that Cyp1a protein was mainly expressed in the cytoplasm of liver cells. Furthermore, our transgenic fish embryos demonstrated that TCDD exposure can regulate the expression levels of several tumor-related factors, including epidermal growth factor, TNF-α, C-myc, proliferating cell nuclear antigen, TGF-β, serine/threonine kinase (Akt), and phosphorylated Akt, suggesting that our transgenic fish can be used as a sensitive model to evaluate the carcinogenicity induced by TCDD exposure.-Luo, J.-J., Su, D.-S., Xie, S.-L., Liu, Y., Liu, P., Yang, X.-J., Pei D.-S. Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish.
|
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
| 2,018 | 5 | 2 | 9 |
20,626,877 |
An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector.
|
This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 x 108 or 1 x 109 genomic copies of AAV1-GFP and 1 x 105 transducing units of LV-dsRed.
|
BMC neuroscience
| 2,010 | 7 | 0 | 7 |
33,255,402 |
Improving Dignity of Care in Community-Dwelling Elderly Patients with Cognitive Decline and Their Caregivers. The Role of Dignity Therapy.
|
Demographic changes have placed age-related mental health disorders at the forefront of public health challenges over the next three decades worldwide. Within the context of cognitive impairment and neurocognitive disorders among elderly people, the fragmentation of the self is associated with existential suffering, loss of meaning and dignity for the patient, as well as with a significant burden for the caregiver. Psychosocial interventions are part of a person-centered approach to cognitive impairment (including early stage dementia and dementia). Dignity therapy (DT) is a therapeutic intervention that has been shown to be effective in reducing existential distress, mood, and anxiety symptoms and improving dignity in persons with cancer and other terminal conditions in palliative care settings. The aims of this paper were: (i) To briefly summarize key issues and challenges related to care in gerontology considering specifically frail elderly/elderly with cognitive decline and their caregivers; and (ii) to provide a narrative review of the recent knowledge and evidence on DT in the elderly population with cognitive impairment. We searched the electronic data base (CINAHL, SCOPUS, PSycInfo, and PubMed studies) for studies regarding the application of DT in the elderly. Additionally, given the caregiver's role as a custodian of diachronic unity of the cared-for and the need to help caregivers to cope with their own existential distress and anticipatory grief, we also propose a DT-dyadic approach addressing the needs of the family as a whole.
|
Behavioral sciences (Basel, Switzerland)
| 2,020 | 11 | 3 | 11 |
25,687,761 |
Small angle X-ray scattering analysis of Cu(2+)-induced oligomers of the Alzheimer's amyloid β peptide.
|
Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid-β peptide (Aβ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu(2+)/Aβ, on the early three-dimensional structures of the Aβ1-40 and Cu(2+)/Aβ1-42 peptides in solution. We found that at molar ratios of 0.5 copper to peptide Aβ1-40 aggregated, while Aβ1-42 adopted a relatively monodisperse cylindrical shape, and at a ratio of 1.5 copper to peptide Aβ1-40 adopted a monodisperse cylindrical shape, while Aβ1-42 adopted the shape of an ellipsoid of rotation. We also found, via in-line rapid mixing SAXS analysis, that both peptides in the absence of copper were monodisperse at very short timeframes (<2 s). Kratky plots of these scattering profiles indicated that immediately after mixing both were intrinsically disordered. Ensemble optimisation modelling reflected this, indicating a wide range of structural conformers. These data reflect the ensembles from which the Cu(2+)-promoted oligomers were derived. Our results are discussed in the light of other studies that have shown that the Cu(2+)/Aβ has a marked effect on fibril and oligomer formation by this peptide, with a higher ratio favouring the formation of cytotoxic non-amyloid oligomers. Our results are relatively consistent with previous two-dimensional studies of the conformations of these Cu(2+)-induced entities, made on a much longer time-scale than SAXS, by transmission electron microscopy and atomic force microscopy, which showed that a range of oligomeric species are formed. We propose that SAXS carried out on a modern synchrotron beamline enables studies on initial events in disordered protein folding on physiologically-relevant time-scales, and will likely provide great insight into the initiating processes of the Aβ misfolding, oligomerisation and amyloid formation.
|
Metallomics : integrated biometal science
| 2,015 | 3 | 0 | 13 |
25,880,443 |
Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease.
|
Fatal familial insomnia (FFI) and a genetic form of Creutzfeldt-Jakob disease (CJD178) are clinically different prion disorders linked to the D178N prion protein (PrP) mutation. The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele, which is thought to influence D178N PrP misfolding, leading to the formation of distinctive prion strains with specific neurotoxic properties. However, the mechanism by which misfolded variants of mutant PrP cause different diseases is not known. We generated transgenic (Tg) mice expressing the mouse PrP homolog of the FFI mutation. These mice synthesize a misfolded form of mutant PrP in their brains and develop a neurological illness with severe sleep disruption, highly reminiscent of FFI and different from that of analogously generated Tg(CJD) mice modeling CJD178. No prion infectivity was detectable in Tg(FFI) and Tg(CJD) brains by bioassay or protein misfolding cyclic amplification, indicating that mutant PrP has disease-encoding properties that do not depend on its ability to propagate its misfolded conformation. Tg(FFI) and Tg(CJD) neurons have different patterns of intracellular PrP accumulation associated with distinct morphological abnormalities of the endoplasmic reticulum and Golgi, suggesting that mutation-specific alterations of secretory transport may contribute to the disease phenotype.
|
PLoS pathogens
| 2,015 | 4 | 6 | 37 |
18,795,266 |
Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat.
|
Positive allosteric modulators of the glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment.
|
Psychopharmacology
| 2,009 | 1 | 3 | 19 |
27,775,225 |
Characterization of Phenotypic and Transcriptional Differences in Human Pluripotent Stem Cells under 2D and 3D Culture Conditions.
|
Human pluripotent stem cells hold great promise for applications in drug discovery and regenerative medicine. Microfluidic technology is a promising approach for creating artificial microenvironments; however, although a proper 3D microenvironment is required to achieve robust control of cellular phenotypes, most current microfluidic devices provide only 2D cell culture and do not allow tuning of physical and chemical environmental cues simultaneously. Here, the authors report a 3D cellular microenvironment plate (3D-CEP), which consists of a microfluidic device filled with thermoresponsive poly(N-isopropylacrylamide)-β-poly(ethylene glycol) hydrogel (HG), which enables systematic tuning of both chemical and physical environmental cues as well as in situ cell monitoring. The authors show that H9 human embryonic stem cells (hESCs) and 253G1 human induced pluripotent stem cells in the HG/3D-CEP system maintain their pluripotent marker expression under HG/3D-CEP self-renewing conditions. Additionally, global gene expression analyses are used to elucidate small variations among different test environments. Interestingly, the authors find that treatment of H9 hESCs under HG/3D-CEP self-renewing conditions results in initiation of entry into the neural differentiation process by induction of PAX3 and OTX1 expression. The authors believe that this HG/3D-CEP system will serve as a versatile platform for developing targeted functional cell lines and facilitate advances in drug screening and regenerative medicine.
|
Advanced healthcare materials
| 2,016 | 11 | 2 | 19 |
33,542,304 |
The nuclear import of the transcription factor MyoD is reduced in mesenchymal stem cells grown in a 3D micro-engineered niche.
|
Smart biomaterials are increasingly being used to control stem cell fate in vitro by the recapitulation of the native niche microenvironment. By integrating experimental measurements with numerical models, we show that in mesenchymal stem cells grown inside a 3D synthetic niche both nuclear transport of a myogenic factor and the passive nuclear diffusion of a smaller inert protein are reduced. Our results also suggest that cell morphology modulates nuclear proteins import through a partition of the nuclear envelope surface, which is a thin but extremely permeable annular portion in cells cultured on 2D substrates. Therefore, our results support the hypothesis that in stem cell differentiation, the nuclear import of gene-regulating transcription factors is controlled by a strain-dependent nuclear envelope permeability, probably related to the reorganization of stretch-activated nuclear pore complexes.
|
Scientific reports
| 2,021 | 2 | 3 | 13 |
21,106,827 |
Retrieval of associative information congruent with prior knowledge is related to increased medial prefrontal activity and connectivity.
|
We remember information that is congruent instead of incongruent with prior knowledge better, but the underlying neural mechanisms related to this enhancement are still relatively unknown. Recently, this memory enhancement due to a prior schema has been suggested to be based on rapid neocortical assimilation of new information, related to optimized encoding and consolidation processes. The medial prefrontal cortex (mPFC) is thought to be important in mediating this process, but its role in retrieval of schema-consistent information is still unclear. In this study, we regarded multisensory congruency with prior knowledge as a schema and used this factor to probe retrieval of consolidated memories either consistent or inconsistent with prior knowledge. We conducted a visuotactile learning paradigm in which participants studied visual motifs randomly associated with word-fabric combinations that were either congruent or incongruent with common knowledge. The next day, participants were scanned using functional magnetic resonance imaging while their memory was tested. Congruent associations were remembered better than incongruent ones. This behavioral finding was parallelized by stronger retrieval-related activity in and connectivity between medial prefrontal and left somatosensory cortex. Moreover, we found a positive across-subject correlation between the connectivity enhancement and the behavioral congruency effect. These results show that successful retrieval of congruent compared to incongruent visuotactile associations is related to enhanced processing in an mPFC-somatosensory network, and support the hypothesis that new information that fits a preexisting schema is more rapidly assimilated in neocortical networks, a process that may be mediated, at least in part, by the mPFC.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,010 | 11 | 3 | 44 |
29,909,983 |
Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features.
|
Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure.
|
Cell
| 2,018 | 7 | 21 | 164 |
26,001,638 |
The transfer function of neuron spike.
|
The mathematical modeling of neuronal signals is a relevant problem in neuroscience. The complexity of the neuron behavior, however, makes this problem a particularly difficult task. Here, we propose a discrete-time linear time-invariant (LTI) model with a rational function in order to represent the neuronal spike detected by an electrode located in the surroundings of the nerve cell. The model is presented as a cascade association of two subsystems: one that generates an action potential from an input stimulus, and one that represents the medium between the cell and the electrode. The suggested approach employs system identification and signal processing concepts, and is dissociated from any considerations about the biophysical processes of the neuronal cell, providing a low-complexity alternative to model the neuronal spike. The model is validated by using in vivo experimental readings of intracellular and extracellular signals. A computational simulation of the model is presented in order to assess its proximity to the neuronal signal and to observe the variability of the estimated parameters. The implications of the results are discussed in the context of spike sorting.
|
Neural networks : the official journal of the International Neural Network Society
| 2,015 | 8 | 0 | 2 |
24,183,013 |
The neuron identity problem: form meets function.
|
A complete understanding of nervous system function cannot be achieved without the identification of its component cell types. In this Perspective, we explore a series of related issues surrounding cell identity and how revolutionary methods for labeling and probing specific neuronal types have clarified this question. Specifically, we ask the following questions: what is the purpose of such diversity, how is it generated, how is it maintained, and, ultimately, how can one unambiguously identity one cell type from another? We suggest that each cell type can be defined by a unique and conserved molecular ground state that determines its capabilities. We believe that gaining an understanding of these molecular barcodes will advance our ability to explore brain function, enhance our understanding of the biochemical basis of CNS disorders, and aid in the development of novel therapeutic strategies.
|
Neuron
| 2,013 | 10 | 9 | 57 |
33,612,000 |
The gender-binary cycle: the perpetual relations between a biological-essentialist view of gender, gender ideology, and gender-labelling and sorting.
|
Gender inequality is one of the most pressing issues of our time. A core factor that feeds gender inequality is people's gender ideology-a set of beliefs about the proper order of society in terms of the roles women and men should fill. We argue that gender ideology is shaped, in large parts, by the way people make sense of gender differences. Specifically, people often think of gender differences as expressions of a predetermined biology, and of men and women as different 'kinds'. We describe work suggesting that thinking of gender differences in this
|
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
| 2,021 | 4 | 11 | 33 |
32,030,781 |
Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus.
|
Clinical guidance is often sought when prescribing drugs for patients with primary mitochondrial disease. Theoretical considerations concerning drug safety in patients with mitochondrial disease may lead to unnecessary withholding of a drug in a situation of clinical need. The aim of this study was to develop consensus on safe medication use in patients with a primary mitochondrial disease. A panel of 16 experts in mitochondrial medicine, pharmacology, and basic science from six different countries was established. A modified Delphi technique was used to allow the panellists to consider draft recommendations anonymously in two Delphi rounds with predetermined levels of agreement. This process was supported by a review of the available literature and a consensus conference that included the panellists and representatives of patient advocacy groups. A high level of consensus was reached regarding the safety of all 46 reviewed drugs, with the knowledge that the risk of adverse events is influenced both by individual patient risk factors and choice of drug or drug class. This paper details the consensus guidelines of an expert panel and provides an important update of previously established guidelines in safe medication use in patients with primary mitochondrial disease. Specific drugs, drug groups, and clinical or genetic conditions are described separately as they require special attention. It is important to emphasise that consensus-based information is useful to provide guidance, but that decisions related to drug prescribing should always be tailored to the specific needs and risks of each individual patient. We aim to present what is current knowledge and plan to update this regularly both to include new drugs and to review those currently included.
|
Journal of inherited metabolic disease
| 2,020 | 7 | 8 | 43 |
30,149,333 |
Depression and chronic diseases: Co-occurrence and communality of risk factors.
|
The aim of current study is to assess the cross-sectional association of chronic non-communicable diseases (diabetes mellitus, arthritis, asthma, chronic lung disease, angina, and stroke) with both diagnosed and undiagnosed depression in the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1, a study of adults in six low- and middle-income countries.
|
Journal of affective disorders
| 2,018 | 12 | 10 | 81 |
29,266,810 |
Multimodal approaches to functional connectivity in autism spectrum disorders: An integrative perspective.
|
Atypical functional connectivity has been implicated in autism spectrum disorders (ASDs). However, the literature to date has been largely inconsistent, with mixed and conflicting reports of hypo- and hyper-connectivity. These discrepancies are partly due to differences between various neuroimaging modalities. Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and magnetoencephalography (MEG) measure distinct indices of functional connectivity (e.g., blood-oxygenation level-dependent [BOLD] signal vs. electrical activity). Furthermore, each method has unique benefits and disadvantages with respect to spatial and temporal resolution, vulnerability to specific artifacts, and practical implementation. Thus far, functional connectivity research on ASDs has remained almost exclusively unimodal; therefore, interpreting findings across modalities remains a challenge. Multimodal integration of fMRI, EEG, and MEG data is critical in resolving discrepancies in the literature, and working toward a unifying framework for interpreting past and future findings. This review aims to provide a theoretical foundation for future multimodal research on ASDs. First, we will discuss the merits and shortcomings of several popular theories in ASD functional connectivity research, using examples from the literature to date. Next, the neurophysiological relationships between imaging modalities, including their relationship with invasive neural recordings, will be reviewed. Finally, methodological approaches to multimodal data integration will be presented, and their future application to ASDs will be discussed. Analyses relating transient patterns of neural activity ("states") are particularly promising. This strategy provides a comparable measure across modalities, captures complex spatiotemporal patterns, and is a natural extension of recent dynamic fMRI research in ASDs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 456-473, 2018.
|
Developmental neurobiology
| 2,018 | 5 | 12 | 37 |
20,713,562 |
Ten years of chronic cluster--attacks still cluster.
|
The chronic variant can be found in 10-20% of all cluster headache patients. While circadian and circannual rhythmicity are characteristic of the episodic variant, little is known on chronobiology in chronic cluster headache. We report a patient with chronic cluster evolved from episodic who recorded a total of 5447 attacks over 10 years. After spectral analysis, cosinor models were calculated within the frequency ranges of 23-25 h (circadian) and 11-13 months (circannual), respectively. Significant results (P < 0.01) were found for 24-h periods, but not for circannual intervals (12 months). However, with regard to circannual periodicity, a semi-circannual rhythm (5-7 months) was suitable for curve fit and yielded significant results in the cosinor analysis at 6 months (P < 0.05). This remarkable long observation period of 10 years shows that, at least for secondary chronic cluster headache which evolved from the episodic form, a typical circadian and circannual rhythmicity comparable to that of episodic cluster headache exists.
|
Cephalalgia : an international journal of headache
| 2,010 | 9 | 0 | 4 |
32,034,695 |
Nickel-Induced Developmental Neurotoxicity in C. elegans Includes Cholinergic, Dopaminergic and GABAergic Degeneration, Altered Behaviour, and Increased SKN-1 Activity.
|
Nickel (Ni) is a ubiquitous metal in the environment with increasing industrial application. While environmental and occupational exposure to Ni compounds has been known to result in toxicities to several organs, including the liver, kidney, lungs, skin and gonads, neurotoxic effects have not been extensively investigated. In this present study, we investigated specific neuronal susceptibility in a C. elegans model of acute Ni neurotoxicity. Wild-type worms and worms expressing green fluorescent protein (GFP) in either cholinergic, dopaminergic or GABAergic neurons were treated with NiCl
|
Neurotoxicity research
| 2,020 | 4 | 9 | 46 |
19,521,663 |
Depression and antidepressants: molecular and cellular aspects.
|
Clinical depression is viewed as a physical and psychic disease process having a neuropathological basis, although a clear understanding of its ethiopathology is still missing. The observation that depressive symptoms are influenced by pharmacological manipulation of monoamines led to the hypothesis that depression results from reduced availability or functional deficiency of monoaminergic transmitters in some cerebral regions. However, there are limitations to current monoamine theories related to mood disorders. Recently, a growing body of experimental data has showed that other classes of endogenous compounds, such as neuropeptides and amino acids, may play a significant role in the pathophysiology of affective disorders. With the development of neuroscience, neuronal networks and intracellular pathways have been identified and characterized, describing the existence of the interaction between monoamines and receptors in turn able to modulate the expression of intracellular proteins and neurotrophic factors, suggesting that depression/antidepressants may be intermingled with neurogenesis/neurodegenerative processes.
|
Cellular and molecular life sciences : CMLS
| 2,009 | 9 | 3 | 32 |
28,770,403 |
Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate: Data from the Efficacy of Nitric Oxide in Stroke Randomised Controlled Trial.
|
Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke. Clinical Trial Registration Clinical Trial Registration-URL: http://www.controlled-trials.com . Unique identifier: ISRCTN99414122.
|
Translational stroke research
| 2,018 | 4 | 0 | 6 |
31,570,534 |
Toward Robust Functional Neuroimaging Genetics of Cognition.
|
A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,019 | 10 | 4 | 14 |
27,989,963 |
Tuning constitutive and pathological inflammation in the gut via the interaction of dietary nitrate and polyphenols with host microbiome.
|
Chronic inflammation is currently recognized as a critical process in modern-era epidemics such as diabetes, obesity and neurodegeneration. However, little attention is paid to the constitutive inflammatory pathways that operate in the gut and that are mandatory for local welfare and the prevention of such multi-organic diseases. Hence, the digestive system, while posing as a barrier between the external environment and the host, is crucial for the balance between constitutive and pathological inflammatory events. Gut microbiome, a recently discovered organ, is now known to govern the interaction between exogenous agents and the host with ensued impact on local and systemic homeostasis. Whereas gut microbiota may be modulated by a myriad of factors, diet constitutes one of its major determinants. Thus, dietary compounds that influence microbial flora may thereby impact on inflammatory pathways. One such example is the redox environment in the gut lumen which is highly dependent on the local generation of nitric oxide along the nitrate-nitrite-nitric oxide pathway and that is further enhanced by simultaneous consumption of polyphenols. In this paper, different pathways encompassing the interaction of dietary nitrate and polyphenols with gut microbiota will be presented and discussed in connection with local and systemic inflammatory events. Furthermore, it will be discussed how these interactive cycles (nitrate-polyphenols-microbiome) may pose as novel strategies to tackle inflammatory diseases.
|
The international journal of biochemistry & cell biology
| 2,016 | 12 | 0 | 5 |
30,347,373 |
Dioxins as potential risk factors for autism spectrum disorder.
|
Autism spectrum disorder (ASD) has emerged as a major public health concern due to its fast-growing prevalence in recent decades. Environmental factors are thought to contribute substantially to the variance in ASD. Interest in environmental toxins as causes of ASD has arisen due to the high sensitivity of the developing human brain to toxic chemicals, particularly to dioxin and certain dioxin-like compounds (dioxins). As a group of typical persistent organic pollutants, dioxins have been found to exert adverse effects on human brain development. In this paper, we review the evidence for association of exposure to dioxins with neurodevelopmental abnormalities related to ASD based on both human epidemiological and animal studies. It has been documented that exposure to dioxins during critical developmental periods increased risk for ASD. This notion has been demonstrated in different populations exposed to high or background level of dioxins. Furthermore, the effects and mechanisms of action of dioxins relevant to the pathophysiology and pathogenesis of ASD are summarized, describing potential underlying mechanisms linking dioxin exposure with ASD onset. Further studies focusing on effects of prenatal/perinatal exposure to individual dioxin congeners or to mixtures of dioxins on ASD-associated behavioral and neurobiological consequences in animal models, and on the mechanisms of actions of dioxins, are needed in order to better understand how dioxin exposure might contribute to increased risk for ASD.
|
Environment international
| 2,018 | 12 | 5 | 20 |
30,509,565 |
Promoting Axon Regeneration in Adult CNS by Targeting Liver Kinase B1.
|
Liver kinase B1 (LKB1), a downstream effector of cyclic AMP (cAMP)/PKA and phosphatidylinositol 3-kinase (PI3K) pathways, is a determinant for migration and differentiation of many cells, but its role in CNS axon regeneration is unknown. Therefore, LKB1 was overexpressed in sensorimotor cortex of adult mice five days after mid-thoracic spinal cord injury, using an AAV2 vector. Regeneration of corticospinal axons was dramatically enhanced. Next, systemic injection of a mutant-AAV9 vector was used to upregulate LKB1 specifically in neurons. This promoted long-distance regeneration of injured corticospinal fibers into caudal spinal cord in adult mice and regrowth of descending serotonergic and tyrosine hydroxylase immunoreactive axons. Either intracortical or systemic viral delivery of LKB1 significantly improved recovery of locomotor functions in adult mice with spinal cord injury. Moreover, we demonstrated that LKB1 used AMPKα, NUAK1, and ERK as the downstream effectors in the cortex of adult mice. Thus, LKB1 may be a critical factor for enhancing the growth capacity of mature neurons and may be an important molecular target in the treatment of CNS injuries.
|
Molecular therapy : the journal of the American Society of Gene Therapy
| 2,019 | 1 | 3 | 25 |
21,084,613 |
Lower-frequency event-related desynchronization: a signature of late mismatch responses to sounds, which is reduced or absent in children with specific language impairment.
|
Poor discrimination of nonlinguistic sounds has been implicated in language-learning problems in children, but research evidence has been inconsistent. This study included 32 participants with specific language impairment (SLI) and 32 typically developing controls aged 7-16 years. Frequency discrimination thresholds were estimated in a task where participants had to distinguish a higher-frequency tone from a 1000 Hz tone. Neurophysiological responses were assessed in an oddball paradigm. Stimuli were either 1030 or 1200 Hz pure tones (deviants) presented in a series of standard 1000 Hz tones, or syllables (deviant [da] or [bi] in a series of standard /ba/). On the behavioral task, children (7- to 11-year-olds) had high thresholds, regardless of language status, but teenagers (12-16 years) with SLI had higher thresholds than their controls. Conventional analysis of electrophysiological responses showed no difference between groups for the mismatch negativity (MMN), but the late discriminative negativity (LDN) was reduced in amplitude for smaller deviants in participants with SLI. Time-frequency analysis revealed that, whereas the MMN reflected enhanced intertrial coherence in the theta frequency band, the LDN corresponded to a period of event-related desynchronization extending across a wide low-frequency band including delta, theta, and alpha. This manifested as a drop in power in those frequencies, which was marked in the controls but reduced or absent in children with SLI across all stimulus types. This provides compelling evidence for a low-level auditory perceptual impairment in SLI that affects a processing stage after initial detection of a sound change.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,010 | 11 | 1 | 18 |
27,074,574 |
Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells.
|
We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and a proaggregatory action on platelets. These changes were prevented by different antiplatelet agents, aspirin[an inhibitor of cyclooxygenase(COX)-1], DG-041[an antagonist of prostaglandin(PG)E2 EP3 receptor] and ticagrelor (a P2Y12 receptor antagonist). The injection of HT29 cells, exposed to platelets in vitro, into the tail vein of humanized immunodeficient mice led to higher incidence of lung metastasis compared to the injection of untreated HT29 cells. This effect was associated with enhanced systemic biosynthesis of thromboxane(TX)A2 and PGE2in vivo. Platelet COX-1 inhibition by aspirin administration to mice prevented the increased rate of metastasis as well as the enhanced production of TXA2 and PGE2 induced by the in vitro priming of HT29 cells by platelets. In conclusion, targeting platelet COX-1 with low-dose aspirin exerts an antimetastatic action by averting the stem cell mimicry of cancer cells associated with enhanced proaggregatory effects induced by platelet-tumor cell interactions. These effects may be shared by other antiplatelet drugs.
|
Oncotarget
| 2,016 | 5 | 13 | 89 |
18,287,950 |
Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson's model.
|
Pharmacological activation of group III metabotropic glutamate receptors (mGluR) or inhibition of group I mGluR by subtype-selective ligands is neuroprotective in experimental models of Parkinson's disease. The aim of this study was to investigate whether targeting both receptor subtypes simultaneously produces enhanced neuroprotection. Rodents bearing a 6-hydroxydopamine lesion were intranigrally administered either the group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid or the group I mGluR antagonist 2-methyl-6-(phenylethynyl)pyridine, alone or in combination. Coadministration of L-(+)-2-amino-4-phosphonobutyric acid and 2-methyl-6-(phenylethynyl)pyridine resulted in robust nigrostriatal neuroprotection that was significantly increased compared with either compound alone. These data suggest that targeting multiple mGluR subtypes with low doses of selective ligands may provide an enhanced therapeutic response in experimental models of Parkinson's disease.
|
Neuroreport
| 2,008 | 3 | 0 | 13 |
29,292,502 |
Validated multi-step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus.
|
Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of in vivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinson's disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of in vivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience.
|
Journal of neurochemistry
| 2,018 | 4 | 0 | 10 |
33,750,832 |
Amplification of potential thermogenetic mechanisms in cetacean brains compared to artiodactyl brains.
|
To elucidate factors underlying the evolution of large brains in cetaceans, we examined 16 brains from 14 cetartiodactyl species, with immunohistochemical techniques, for evidence of non-shivering thermogenesis. We show that, in comparison to the 11 artiodactyl brains studied (from 11 species), the 5 cetacean brains (from 3 species), exhibit an expanded expression of uncoupling protein 1 (UCP1, UCPs being mitochondrial inner membrane proteins that dissipate the proton gradient to generate heat) in cortical neurons, immunolocalization of UCP4 within a substantial proportion of glia throughout the brain, and an increased density of noradrenergic axonal boutons (noradrenaline functioning to control concentrations of and activate UCPs). Thus, cetacean brains studied possess multiple characteristics indicative of intensified thermogenetic functionality that can be related to their current and historical obligatory aquatic niche. These findings necessitate reassessment of our concepts regarding the reasons for large brain evolution and associated functional capacities in cetaceans.
|
Scientific reports
| 2,021 | 3 | 5 | 12 |
33,807,308 |
Initial Experience of the Levodopa-Entacapone-Carbidopa Intestinal Gel in Clinical Practice.
|
Patients in fluctuating stages of Parkinson's disease (PD) require device-aided treatments. Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) is a well-proven option in clinical practice. We now report the first clinical experience of levodopa-entacapone-carbidopa intestinal gel (LECIG) therapy. An observational study of the first patients to start LECIG in our clinic was performed. Twenty-four patients (11 females, 13 males) were included. The median age was 71.5 years, and the median duration since PD diagnosis was 15.5 years. The median treatment duration was 305 days. Median doses were: 6.0 mL as morning dose, 2.5 mL/h as infusion rate, and 1.0 mL as extra dose. Half of the patients were switched directly from LCIG. These patients express improvements in the size and weight of the pump. Furthermore, most of them considered the new pump to be improved regarding user-friendliness. Six patients discontinued LECIG, three due to diarrhea, one due to hallucinations and two deceased (one cardiac arrest and one COVID-19). LECIG has shown to be possible to use in patients with PD, efficacy and safety as expected. Patients are generally happy with the size and usability of the pump, but some technical improvements of the software are warranted, as well as larger, prospective studies.
|
Journal of personalized medicine
| 2,021 | 3 | 7 | 40 |
28,892,581 |
Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex.
|
Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms.
|
The European journal of neuroscience
| 2,017 | 11 | 2 | 19 |
End of preview. Expand
in Data Studio
Dataset Card for PubMed Citations Dataset
Dataset Description
This dataset contains metadata and citation information for 20,000 neuroscience-related articles indexed by PubMed. The data is intended for tasks related to bibliometrics, scientific impact prediction, citation analysis, and natural language processing on biomedical literature.
Half of the articles have been cited within the first five years following publication, the other half has not.
Dataset Structure
- Format: CSV
- Rows: 20,000 entries
- Columns: 8
| Column Name | Description | Type |
|---|---|---|
pmid |
PubMed ID (unique identifier for each article) | int64 |
title |
Title of the article | string |
abstract |
Abstract text of the article | string |
journal |
Journal where the article was published | string |
pub_year |
Year of publication | int64 |
pub_month |
Month of publication | int64 |
citation_count_within_one_year |
Number of citations within 1 year of publication (from OpenCitations API) | float64 |
citation_count_within_five_years |
Number of citations within 5 years of publication (from OpenCitations API) | float64 |
Example Entry
{
"pmid": 27466332,
"title": "Catecholaminergic Neuromodulation Shapes Intrinsic MRI Functional Connectivity in the Human Brain",
"abstract": "The brain commonly exhibits spontaneous (i.e.,...",
"journal": "The Journal of neuroscience",
"pub_year": 2016,
"pub_month": 7,
"citation_count_within_one_year": 8.0,
"citation_count_within_five_years": 51.0
}
Source Data
- Original source: PubMed
- Citation counts: Retrieved via OpenCitations API
- License: Please check terms of use for PubMed and OpenCitations before redistribution.
Intended Uses
- Predicting citation count based on article metadata and abstract.
- Studying the relationship between article content and citation patterns.
- Benchmarking NLP models on biomedical abstracts.
Dataset Creation
- Articles were sampled from PubMed.
- Citation counts were collected using the OpenCitations API for each pmid.
- Data was cleaned to ensure all entries have complete fields.
Data Splits
No predefined splits. Users may create splits (e.g., train/test/validation) as needed.
Usage Example (Python/Huggingface Datasets)
from datasets import load_dataset
dataset = load_dataset(
"rudyvdbrink/CitationDatabase",
data_files="NeuroscienceCitationDatabase.json",
)
Limitations
- Only includes articles with complete metadata and citation data.
- Citation data is as provided by OpenCitations; coverage may not be exhaustive.
- Abstracts may contain formatting artifacts.
Citation
If you use this dataset, please cite the authors of the articles appropriately.
Contact
- Downloads last month
- 142