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33,926,981 |
Influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder: protocol for a systematic review and meta-analysis.
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Despite available pharmacological and psychological treatments, remission rates for bipolar disorder remain relatively low. Current research implicates the experience of childhood trauma as a potential moderator of poor treatment outcomes among individuals with bipolar disorder. To date, the evidence reporting the influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder has not been systematically reviewed.
|
BMJ open
| 2,021 | 4 | 1 | 1 |
30,451,069 |
Evaluating Cerebrovascular Reactivity during the Early Symptomatic Phase of Sport Concussion.
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Cerebrovascular reactivity (CVR) indexes the ability of blood vessels to respond to vasoactive stimuli and may be a sensitive biomarker of concussion. However, alterations in whole-brain CVR remain poorly understood during the early symptomatic phase of injury. In this study, CVR was assessed using blood-oxygenation-level dependent functional magnetic resonance imaging (BOLD fMRI) combined with a respiratory challenge paradigm; resting cerebral blood flow (CBF) was also evaluated using arterial spin labeling (ASL). Imaging data were collected for 77 university-level athletes, including 56 athletic uninjured controls and 21 concussed athletes scanned in the early symptomatic phase of injury (≤7 days post-injury). The normal response to respiratory challenge was assessed in the athletic control group, in which a robust whole-brain response was observed. The concussed athletes were then compared to a matched subset of controls. Concussion was associated with greater reductions in BOLD activity during the early phase of the respiratory task, localized primarily in frontal and pre-frontal areas, whereas no significant effects on resting global CBF were observed. In addition, greater symptom severity was associated with greater reductions in BOLD response, with effects distributed throughout the brain. This study establishes fMRI with respiratory challenge as a robust method for assessing acute concussion-related alterations in CVR. Moreover, it highlights the importance of examining neurovascular response to physiological stressors after a concussion.
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Journal of neurotrauma
| 2,019 | 5 | 2 | 18 |
24,356,107 |
Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells.
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Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion-derived spheres.
|
Neuroreport
| 2,014 | 5 | 1 | 4 |
33,314,443 |
Extended-amygdala intrinsic functional connectivity networks: A population study.
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Pre-clinical and human neuroimaging research implicates the extended-amygdala (ExtA) (including the bed nucleus of the stria terminalis [BST] and central nucleus of the amygdala [CeA]) in networks mediating negative emotional states associated with stress and substance-use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised a large sample (n > 1,000 healthy young adult humans) to compare the intrinsic functional connectivity networks (ICNs) of the BST and CeA using task-free functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. We assessed whether inter-individual differences within these ICNs were related to two principal components representing negative disposition and alcohol use. Building on recent primate evidence, we tested whether within BST-CeA intrinsic functional connectivity (iFC) was heritable and further examined co-heritability with our principal components. We demonstrate the BST and CeA to have discrete, but largely overlapping ICNs similar to previous findings. We found no evidence that within BST-CeA iFC was heritable; however, post hoc analyses found significant BST iFC heritability with the broader superficial and centromedial amygdala regions. There were no significant correlations or co-heritability associations with our principal components either across the ICNs or for specific BST-Amygdala iFC. Possible differences in phenotype associations across task-free, task-based, and clinical fMRI are discussed, along with suggestions for more causal investigative paradigms that make use of the now well-established ExtA ICNs.
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Human brain mapping
| 2,021 | 4 | 1 | 4 |
30,831,159 |
Biophysical mechanisms underlying the membrane trafficking of synaptic adhesion molecules.
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Adhesion proteins play crucial roles at synapses, not only by providing a physical trans-synaptic linkage between axonal and dendritic membranes, but also by connecting to functional elements including the pre-synaptic neurotransmitter release machinery and post-synaptic receptors. To mediate these functions, adhesion proteins must be organized on the neuronal surface in a precise and controlled manner. Recent studies have started to describe the mobility, nanoscale organization, and turnover rate of key synaptic adhesion molecules including cadherins, neurexins, neuroligins, SynCAMs, and LRRTMs, and show that some of these proteins are highly mobile in the plasma membrane while others are confined at sub-synaptic compartments, providing evidence for different regulatory pathways. In this review article, we provide a biophysical view of the diffusional trapping of adhesion molecules at synapses, involving both extracellular and intracellular protein interactions. We review the methodology underlying these measurements, including biomimetic systems with purified adhesion proteins, means to perturb protein expression or function, single molecule imaging in cultured neurons, and analytical models to interpret the data. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.
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Neuropharmacology
| 2,020 | 6 | 4 | 13 |
29,945,903 |
Actin filaments partition primary cilia membranes into distinct fluid corrals.
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Physical properties of primary cilia membranes in living cells were examined using two independent, high-spatiotemporal-resolution approaches: fast tracking of single quantum dot-labeled G protein-coupled receptors and a novel two-photon super-resolution fluorescence recovery after photobleaching of protein ensemble. Both approaches demonstrated the cilium membrane to be partitioned into corralled domains spanning 274 ± 20 nm, within which the receptors are transiently confined for 0.71 ± 0.09 s. The mean membrane diffusion coefficient within the corrals,
|
The Journal of cell biology
| 2,018 | 8 | 6 | 36 |
24,991,962 |
Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis.
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Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fear-inducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3.
|
Neuron
| 2,014 | 7 | 11 | 163 |
23,804,090 |
Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons.
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The embryonic sympathetic nervous system consists of predominantly noradrenergic neurons and a very small population of cholinergic neurons. Postnatal development further allows target-dependent switch of a subset of noradrenergic neurons into cholinergic phenotype. How embryonic cholinergic neurons are specified at the prenatal stages remains largely unknown. In this study, we found that the expression of transcription factor Tlx3 was progressively restricted to a small population of embryonic sympathetic neurons in mice. Immunostaining for vesicular acetylcholine transporter (VAChT) showed that Tlx3 was highly expressed in cholinergic neurons at the late embryonic stage E18.5. Deletion of Tlx3 resulted in the loss of Vacht expression at E18.5 but not E12.5. By contrast, Tlx3 was required for expression of the cholinergic peptide vasoactive intestinal polypeptide (VIP), and somatostatin (SOM) at both E12.5 and E18.5. Furthermore, we found that, at E18.5 these putative cholinergic neurons expressed glial cell line-derived neurotrophic factor family coreceptor Ret but not tyrosine hydroxylase (Ret(+)/TH(-)). Deletion of Tlx3 also resulted in disappearance of high-level Ret expression. Last, unlike Tlx3, Ret was required for the expression of VIP and SOM at E18.5 but not E12.5. Together, these results indicate that transcription factor Tlx3 is required for the acquisition of cholinergic phenotype at the late embryonic stage as well as the expression and maintenance of cholinergic peptides VIP and SOM throughout prenatal development of mouse sympathetic neurons.
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The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,013 | 6 | 0 | 9 |
33,319,744 |
Comprehension of computer code relies primarily on domain-general executive brain regions.
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Computer programming is a novel cognitive tool that has transformed modern society. What cognitive and neural mechanisms support this skill? Here, we used functional magnetic resonance imaging to investigate two candidate brain systems: the multiple demand (MD) system, typically recruited during math, logic, problem solving, and executive tasks, and the language system, typically recruited during linguistic processing. We examined MD and language system responses to code written in Python, a text-based programming language (Experiment 1) and in ScratchJr, a graphical programming language (Experiment 2); for both, we contrasted responses to code problems with responses to content-matched sentence problems. We found that the MD system exhibited strong bilateral responses to code in both experiments, whereas the language system responded strongly to sentence problems, but weakly or not at all to code problems. Thus, the MD system supports the use of novel cognitive tools even when the input is structurally similar to natural language.
|
eLife
| 2,020 | 12 | 15 | 66 |
21,671,841 |
Retrospective chart review of duloxetine and pregabalin in the treatment of painful neuropathy.
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The primary aims of our study were to compare pregabalin and duloxetine in a neuromuscular clinic for diabetic neuropathic pain (DPN) and to study the effect of these medications in cryptogenic sensory polyneuropathy. We performed a retrospective chart review of 143 patients who were started on pregabalin or duloxetine during a 10-month period in a tertiary neuromuscular outpatient center for neuropathic pain. Duloxetine and pregabalin were started in 103 and 91 patients, respectively. Ninety-two patients tried only one of the two medications while both medications were used at different time periods in 51 patients. Follow-up was available for 87 patients on pregabalin and 89 patients on duloxetine. More patients with neuropathic pain reported an improvement with pregabalin (33%) than duloxetine (21%). Duloxetine (38%) had a higher frequency of side effects compared to pregabalin (30%). However, these differences between pregabalin and duloxetine were not statistically significant. Despite the study's limitations of retrospective design, these findings suggest that both pregabalin and duloxetine are probably effective for neuropathic pain, secondary to diabetes or cryptogenic sensory peripheral neuropathy in a tertiary care academic neuromuscular center. Prospective randomized controlled comparative effectiveness studies are required for both drugs in the treatment of neuropathic pain.
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The International journal of neuroscience
| 2,011 | 9 | 3 | 10 |
34,193,913 |
Examining early structural and functional brain alterations in postpartum depression through multimodal neuroimaging.
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Postpartum depression (PPD) affects approximately 1 in 10 women after childbirth. A thorough understanding of a preexisting vulnerability to PPD will likely aid the early detection and treatment of PPD. Using a within-sample association, the study examined whether the brain's structural and functional alterations predict the onset of depression. 157 euthymic postpartum women were subjected to a multimodal MRI scan within the first 6 days of childbirth and were followed up for 12 weeks. Based on a clinical interview 12 weeks postpartum, participants were classified as mentally healthy or having either PPD or adjustment disorder (AD). Voxel-based morphometry and resting-state functional connectivity comparisons were performed between the three groups. 13.4% of women in our study developed PPD (n = 21) and 12.1% (n = 19) adjustment disorder (AD). The risk factors for PPD were a psychiatric history and the experience and severity of baby blues and the history of premenstrual syndrome. Despite the different risk profiles, no differences between the PPD, AD and control group were apparent based on structural and functional neuroimaging data immediately after childbirth. At 12 weeks postpartum, a significant association was observed between Integrated Local Correlation (LCor) and the Edinburgh Postnatal Depression Score (EPDS). Our findings do not support the notion that the brain's structural and resting-state functional alterations, if present, can be used as an early biomarker of PPD or AD. However, effects may become apparent if continuous measures of symptom severity are chosen.
|
Scientific reports
| 2,021 | 6 | 4 | 16 |
28,993,204 |
A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells.
|
Recent progress in electrophysiological and optical methods for neuronal recordings provides vast amounts of high-resolution data. In parallel, the development of computer technology has allowed simulation of ever-larger neuronal circuits. A challenge in taking advantage of these developments is the construction of single-cell and network models in a way that faithfully reproduces neuronal biophysics with subcellular level of details while keeping the simulation costs at an acceptable level.
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Journal of neuroscience methods
| 2,018 | 1 | 2 | 20 |
24,943,843 |
Distinct fusion properties of synaptotagmin-1 and synaptotagmin-7 bearing dense core granules.
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Adrenal chromaffin cells release hormones and neuropeptides that are essential for physiological homeostasis. During this process, secretory granules fuse with the plasma membrane and deliver their cargo to the extracellular space. It was once believed that fusion was the final regulated step in exocytosis, resulting in uniform and total release of granule cargo. Recent evidence argues for nonuniform outcomes after fusion, in which cargo is released with variable kinetics and selectivity. The goal of this study was to identify factors that contribute to the different outcomes, with a focus on the Ca(2+)-sensing synaptotagmin (Syt) proteins. Two Syt isoforms are expressed in chromaffin cells: Syt-1 and Syt-7. We find that overexpressed and endogenous Syt isoforms are usually sorted to separate secretory granules and are differentially activated by depolarizing stimuli. In addition, overexpressed Syt-1 and Syt-7 impose distinct effects on fusion pore expansion and granule cargo release. Syt-7 pores usually fail to expand (or reseal), slowing the dispersal of lumenal cargo proteins and granule membrane proteins. On the other hand, Syt-1 diffuses from fusion sites and promotes the release of lumenal cargo proteins. These findings suggest one way in which chromaffin cells may regulate cargo release is via differential activation of synaptotagmin isoforms.
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Molecular biology of the cell
| 2,014 | 8 | 2 | 24 |
20,927,333 |
Delayed onset of experimental autoimmune encephalomyelitis in Olig1 deficient mice.
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Olig1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated.
|
PloS one
| 2,010 | 9 | 2 | 22 |
20,510,586 |
Coping flexibility in young adults: comparison between subjects with and without schizotypal personality features.
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The current study examined characteristics of coping patterns adopted by college students in mainland China. In particular, it examined the coping strategies adopted by subjects with schizotypal personality (SPD) features compared to those without SPD features, and compared the relative effectiveness of their coping. Four types of coping flexibility were identified among the college sample (n=427), including active-inflexible, passive-inflexible, active-inconsistent, and passive-inconsistent styles. The passive-inconsistent style was related to the worst outcomes. When comparing subjects with SPD features with those without SPD features, subjects with SPD features endorsed significantly more emotion-focused strategies in uncontrollable situations than those without SPD features. The SPD group experienced higher levels of trait anxiety, depression, paranoid ideation and general health problems. The SPD group also generally perceived more, less controllable stress than the non-SPD group and randomly used all four categories of coping strategies.
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Schizophrenia research
| 2,010 | 9 | 0 | 9 |
30,430,321 |
Social Conformity in Autism.
|
Humans are extremely susceptible to social influence. Here, we examine whether this susceptibility is altered in autism, a condition characterized by social difficulties. Autistic participants (N = 22) and neurotypical controls (N = 22) completed a memory test of previously seen words and were then exposed to answers supposedly given by four other individuals. Autistic individuals and controls were as likely to alter their judgements to align with inaccurate responses of group members. These changes reflected both temporary judgement changes (public conformity) and long-lasting memory changes (private conformity). Both groups were more susceptible to answers believed to be from other humans than from computer algorithms. Our results suggest that autistic individuals and controls are equally susceptible to social influence when reporting their memories.
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Journal of autism and developmental disorders
| 2,019 | 3 | 1 | 12 |
28,546,077 |
Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice.
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The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission. Recently, l-KYN or one of its derivatives were attributed a direct role in the regulation of the systemic circulation. l-KYN dilates arterial blood vessels during sepsis in rats, while it increases cerebral blood flow (CBF) in awake rabbits. Therefore, we hypothesized that acute elevation of systemic l-KYN concentration may exert potential effects on mean arterial blood pressure (MABP) and on resting CBF in the mouse brain. C57Bl/6 male mice were anesthetized with isoflurane, and MABP was monitored in the femoral artery, while CBF was assessed through the intact parietal bone with the aid of laser speckle contrast imaging. l-KYN sulfate (l-KYNs) (300mg/kg, i.p.) or vehicle was administered intraperitoneally. Subsequently, MABP and CBF were continuously monitored for 2.5h. In the control group, MABP and CBF were stable (69±4mmHg and 100±5%, respectively) throughout the entire data acquisition period. In the l-KYNs-treated group, MABP was similar to that, of control group (73±6mmHg), while hypoperfusion transients of 22±6%, lasting 7±3min occurred in the cerebral cortex over the first 60-120min following drug administration. In conclusion, the systemic high-dose of l-KYNs treatment destabilizes resting CBF by inducing a number of transient hypoperfusion events. This observation indicates the careful consideration of the dose of l-KYN administration by interpreting the effect of kynurenergic manipulation on brain function. By planning clinical trials basing on kynurenergic manipulation possible vascular side effects should also be considered.
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Microvascular research
| 2,017 | 11 | 0 | 4 |
31,642,807 |
Neural precursors of decisions that matter-an ERP study of deliberate and arbitrary choice.
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The readiness potential (RP)-a key ERP correlate of upcoming action-is known to precede subjects' reports of their decision to move. Some view this as evidence against a causal role for consciousness in human decision-making and thus against free-will. But previous work focused on arbitrary decisions-purposeless, unreasoned, and without consequences. It remains unknown to what degree the RP generalizes to deliberate, more ecological decisions. We directly compared deliberate and arbitrary decision-making during a $1000-donation task to non-profit organizations. While we found the expected RPs for arbitrary decisions, they were strikingly absent for deliberate ones. Our results and drift-diffusion model are congruent with the RP representing accumulation of noisy, random fluctuations that drive arbitrary-but not deliberate-decisions. They further point to different neural mechanisms underlying deliberate and arbitrary decisions, challenging the generalizability of studies that argue for no causal role for consciousness in decision-making to real-life decisions.
|
eLife
| 2,019 | 10 | 5 | 44 |
24,697,290 |
Discovery of a neuroprotective chemical, (S)-N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties.
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(-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form. It is nontoxic, orally bioavailable, metabolically stable, and able to cross the blood-brain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury.
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Journal of medicinal chemistry
| 2,014 | 5 | 6 | 34 |
30,035,325 |
Resilience predicts remission in antidepressant treatment of geriatric depression.
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With the world population rapidly aging, it is increasingly important to identify sociodemographic, cognitive, and clinical features that predict poor outcome in geriatric depression. Self-report measures of resilience-ie, the ability to adapt and thrive in the face of adversity-may identify those depressed older adults with more favorable prognoses.
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International journal of geriatric psychiatry
| 2,018 | 12 | 5 | 17 |
24,744,858 |
Influence of cutaneous and muscular circulation on spatially resolved versus standard Beer-Lambert near-infrared spectroscopy.
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The potential interference of cutaneous circulation on muscle blood volume and oxygenation monitoring by near-infrared spectroscopy (NIRS) remains an important limitation of this technique. Spatially resolved spectroscopy (SRS) was reported to minimize the contribution of superficial tissue layers in cerebral monitoring but this characteristic has never been documented in muscle tissue monitoring. This study aims to compare SRS with the standard Beer-Lambert (BL) technique in detecting blood volume changes selectively induced in muscle and skin. In 16 healthy subjects, the biceps brachii was investigated during isometric elbow flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed before and after exposure of the upper arm to warm air flow. From probes applied over the muscle belly the following variables were recorded: total hemoglobin index (THI, SRS-based), total hemoglobin concentration (tHb, BL-based), tissue oxygenation index (TOI, SRS-based), and skin blood flow (SBF), using laser Doppler flowmetry. Blood volume indices exhibited similar changes during muscle contraction but only tHb significantly increased during warming (+5.2 ± 0.7 μmol/L·cm, an effect comparable to the increase occurring in postcontraction hyperemia), accompanying a 10-fold increase in SBF. Contraction-induced changes in tHb and THI were not substantially affected by warming, although the tHb tracing was shifted upward by (5.2 ± 3.5 μmol/L·cm, P < 0.01). TOI was not affected by cutaneous warming. In conclusion, SRS appears to effectively reject interference by SBF in both muscle blood volume and oxygenation monitoring. Instead, BL-based parameters should be interpreted with caution, whenever changes in cutaneous perfusion cannot be excluded.
|
Physiological reports
| 2,013 | 12 | 1 | 25 |
28,236,843 |
Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity.
|
The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in multiple sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants. A prospective hypothesis is suggested here in which exposure to air pollutants may initiate destructive mechanisms inducing inflammatory-oxidative cascades, reduction of immunological self-tolerance and neurodegeneration leading to brain autoimmunity.
|
Medical hypotheses
| 2,017 | 3 | 3 | 28 |
30,902,980 |
Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism.
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Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In vertebrates, SREBP activation is mainly controlled by a complex and well-characterized feedback mechanism mediated by cholesterol, a crucial bio-product of the SREBP-activated mevalonate pathway. In this work, we identified acto-myosin contractility and mechanical forces imposed by the extracellular matrix (ECM) as SREBP1 regulators. SREBP1 control by mechanical cues depends on geranylgeranyl pyrophosphate, another key bio-product of the mevalonate pathway, and impacts on stem cell fate in mouse and on fat storage in Drosophila. Mechanistically, we show that activation of AMP-activated protein kinase (AMPK) by ECM stiffening and geranylgeranylated RhoA-dependent acto-myosin contraction inhibits SREBP1 activation. Our results unveil an unpredicted and evolutionary conserved role of SREBP1 in rewiring cell metabolism in response to mechanical cues.
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Nature communications
| 2,019 | 3 | 9 | 150 |
31,129,368 |
Delayed cortical maturation at the centrotemporal brain regions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS).
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Benign childhood epilepsy with centrotemporal spikes (BCECTS) is an epilepsy syndrome commonly found in child and adolescent. Although the prognosis is mostly favorable as long as the seizure is well controlled. However, they are often suffering from the cognitive and behavioral problems which might be the consequences of the initial insults. It is still not clear whether the initial epileptiform discharges has long term impact on the resting-state brain activities at later ages. This study investigated the resting-state brain activities in BCECTS patients with clinical seizure remission stage (n = 16; 11 males) and compared with the non-epileptic, age-matched control subjects. Quantitative electroencephalography (qEEG) revealed a significantly higher absolute power of the theta and alpha waves in BCECTS patients with clinical seizure remission as compared with the non-epileptic control subjects. Interestingly, the differences were observed mainly over the centrotemporal electrodes which are the common sites of the initial epileptiform discharges. The differences were more significant in patients with bilateral epileptiform discharges than those with the unilateral epileptic activities. Typically, the brain wave power continuously decreases with increasing ages. Therefore, higher absolute powers of the brain waves indicate more delayed in cortical maturation compared with the non-epileptic control group. These findings indicated that BCECTS patients have delay cortical maturation at the centrotemporal brain regions even at the clinical seizure remission phase.
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Epilepsy research
| 2,019 | 8 | 0 | 2 |
25,805,403 |
Factor structure and reliability of the Italian adaptation of the Hypomania Check List-32, second revision (HCL-32-R2).
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To assess the psychometric properties of the Italian adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) treatment-seeking outpatients.
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Journal of affective disorders
| 2,015 | 6 | 1 | 10 |
32,184,415 |
The expression level of alpha-synuclein in different neuronal populations is the primary determinant of its prion-like seeding.
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Alpha-synuclein (aSyn)-rich aggregates propagate in neuronal networks and compromise cellular homeostasis leading to synucleinopathies such as Parkinson's disease. Aggregated aSyn spread follows a conserved spatio-temporal pattern that is not solely dependent on connectivity. Hence, the differential tropism of aSyn-rich aggregates to distinct brain regions, or their ability to amplify within those regions, must contribute to this process. To better understand what underlies aSyn-rich aggregates distribution within the brain, we generated primary neuronal cultures from various brain regions of wild-type mice and mice expressing a reduced level of aSyn, and exposed them to fibrillar aSyn. We then assessed exogenous fibrillar aSyn uptake, endogenous aSyn seeding, and endogenous aSyn physiological expression levels. Despite a similar uptake of exogenous fibrils by neuronal cells from distinct brain regions, the seeded aggregation of endogenous aSyn differed greatly from one neuronal population to another. The different susceptibility of neuronal populations was linked to their aSyn expression level. Our data establish that endogenous aSyn expression level plays a key role in fibrillar aSyn prion-like seeding, supporting that endogenous aSyn expression level participates in selective regional brain vulnerability.
|
Scientific reports
| 2,020 | 3 | 7 | 58 |
23,200,194 |
Using a million cell simulation of the cerebellum: network scaling and task generality.
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Several factors combine to make it feasible to build computer simulations of the cerebellum and to test them in biologically realistic ways. These simulations can be used to help understand the computational contributions of various cerebellar components, including the relevance of the enormous number of neurons in the granule cell layer. In previous work we have used a simulation containing 12000 granule cells to develop new predictions and to account for various aspects of eyelid conditioning, a form of motor learning mediated by the cerebellum. Here we demonstrate the feasibility of scaling up this simulation to over one million granule cells using parallel graphics processing unit (GPU) technology. We observe that this increase in number of granule cells requires only twice the execution time of the smaller simulation on the GPU. We demonstrate that this simulation, like its smaller predecessor, can emulate certain basic features of conditioned eyelid responses, with a slight improvement in performance in one measure. We also use this simulation to examine the generality of the computation properties that we have derived from studying eyelid conditioning. We demonstrate that this scaled up simulation can learn a high level of performance in a classic machine learning task, the cart-pole balancing task. These results suggest that this parallel GPU technology can be used to build very large-scale simulations whose connectivity ratios match those of the real cerebellum and that these simulations can be used guide future studies on cerebellar mediated tasks and on machine learning problems.
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Neural networks : the official journal of the International Neural Network Society
| 2,013 | 11 | 0 | 16 |
28,377,175 |
Tactile object categories can be decoded from the parietal and lateral-occipital cortices.
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The visual system classifies objects into categories, and distinct populations of neurons within the temporal lobe respond preferentially to objects of a given perceptual category. We can also classify the objects we recognize with the sense of touch, but less is known about the neuronal correlates underlying this cognitive function. To address this question, we performed a multivariate pattern analysis (MVPA) of functional magnetic resonance imagining (fMRI) activity to identify the cortical areas that can be used to decode the category of objects explored with the hand. We observed that tactile object category can be decoded from the activity patterns of somatosensory and parietal areas. Importantly, we found that categories can also be decoded from the lateral occipital complex (LOC), which is a multimodal region known to be related to the representation of object shape. Furthermore, a hyperalignment analysis showed that activity patterns are similar across subjects. Our results thus indicate that tactile object recognition generates category-specific patterns of activity in a multisensory area known to encode objects, and that these patterns have a similar functional organization across individuals.
|
Neuroscience
| 2,017 | 6 | 0 | 7 |
24,549,293 |
Accurate metacognition for visual sensory memory representations.
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The capacity to attend to multiple objects in the visual field is limited. However, introspectively, people feel that they see the whole visual world at once. Some scholars suggest that this introspective feeling is based on short-lived sensory memory representations, whereas others argue that the feeling of seeing more than can be attended to is illusory. Here, we investigated this phenomenon by combining objective memory performance with subjective confidence ratings during a change-detection task. This allowed us to compute a measure of metacognition--the degree of knowledge that subjects have about the correctness of their decisions--for different stages of memory. We show that subjects store more objects in sensory memory than they can attend to but, at the same time, have similar metacognition for sensory memory and working memory representations. This suggests that these subjective impressions are not an illusion but accurate reflections of the richness of visual perception.
|
Psychological science
| 2,014 | 4 | 2 | 24 |
17,627,942 |
Exocytotic release of ATP from cultured astrocytes.
|
Astrocytes appear to communicate with each other as well as with neurons via ATP. However, the mechanisms of ATP release are controversial. To explore whether stimuli that increase [Ca(2+)](i) also trigger vesicular ATP release from astrocytes, we labeled ATP-containing vesicles with the fluorescent dye quinacrine, which exhibited a significant co-localization with atrial natriuretic peptide. The confocal microscopy study revealed that quinacrine-loaded vesicles displayed mainly non-directional spontaneous mobility with relatively short track lengths and small maximal displacements, whereas 4% of vesicles exhibited directional mobility. After ionomycin stimulation only non-directional vesicle mobility could be observed, indicating that an increase in [Ca(2+)](i) attenuated vesicle mobility. Total internal reflection fluorescence (TIRF) imaging in combination with epifluorescence showed that a high percentage of fluorescently labeled vesicles underwent fusion with the plasma membrane after stimulation with glutamate or ionomycin and that this event was Ca(2+)-dependent. This was confirmed by patch-clamp studies on HEK-293T cells transfected with P2X(3) receptor, used as sniffers for ATP release from astrocytes. Glutamate stimulation of astrocytes was followed by an increase in the incidence of small transient inward currents in sniffers, reminiscent of postsynaptic quantal events observed at synapses. Their incidence was highly dependent on extracellular Ca(2+). Collectively, these findings indicate that glutamate-stimulated ATP release from astrocytes was most likely exocytotic and that after stimulation the fraction of quinacrine-loaded vesicles, spontaneously exhibiting directional mobility, disappeared.
|
The Journal of biological chemistry
| 2,007 | 9 | 11 | 92 |
30,357,316 |
Dopamine Signaling Modulates the Stability and Integration of Intrinsic Brain Networks.
|
Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape regional information processing and large-scale network interactions remains unclear. Here we investigated effects of lowered dopamine levels on within-region temporal signal variability (measured by sample entropy) and between-region functional connectivity (measured by pairwise temporal correlations) in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent resting-state functional MRI (fMRI) scanning. Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared with the balanced control treatment. The analysis captured a pattern of increased regional signal variability following dopamine depletion. Changes in hemodynamic signal variability were concomitant with changes in functional connectivity, such that nodes with greatest increase in signal variability following dopamine depletion also experienced greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopamine-dependent signal variability is critically associated with functional embedding of individual areas in large-scale networks.
|
Cerebral cortex (New York, N.Y. : 1991)
| 2,019 | 1 | 13 | 78 |
28,912,081 |
Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity.
|
Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.
|
NeuroImage
| 2,017 | 11 | 9 | 109 |
29,523,945 |
Comparison of cerebral perfusion in perimesencephalic subarachnoid hemorrhage and aneurysmal subarachnoid hemorrhage.
|
Perimesencephalic hemorrhage (PMH) is a benign subtype of nonaneurysmal subarachnoid hemorrhage (SAH). We aimed to investigate if cerebral perfusion in PMH is less affected than in aneurysmal SAH (aSAH).
|
Neuroradiology
| 2,018 | 6 | 2 | 4 |
26,349,765 |
The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes.
|
The post translational modification of lysine acetylation is a key mechanism that regulates chromatin structure. Epigenetic readers, such as the BET domains, are responsible for reading histone lysine acetylation which is a hallmark of open chromatin structure, further providing a scaffold that can be accessed by RNA polymerases as well as transcription factors. Recently, several reports have assessed and highlighted the roles of epigenetic readers in various cellular contexts. However, little is known about their role in the regulation of inflammatory genes, which is critical in exquisitely tuning inflammatory responses to a variety of immune stimuli. In this study, we investigated the role of epigenetic readers BRD2 and BRD4 in the lipopolysaccharide (LPS)-induced immune responses in mouse primary astrocytes. Inflammatory stimulation by LPS showed that the levels of Brd2 mRNA and protein were increased, while Brd4 mRNA levels did not change. Knocking down of Brd2 mRNA using specific small interfering RNA (siRNA) in cultured mouse primary astrocytes inhibited LPS-induced mRNA expression and secretion of plasminogen activator inhibitor-1 (PAI-1). However, no other pro-inflammatory cytokines, such as Il-6, Il-1β and Tnf-α, were affected. Indeed, treatment with bromodomain-containing protein inhibitor, JQ1, blocked Pai-1 mRNA expression through the inhibition of direct BRD2 protein-binding and active histone modification on Pai-1 promoter. Taken together, our data suggest that BRD2 is involved in the modulation of neuroinflammatory responses through PAI-1 and via the regulation of epigenetic reader BET protein, further providing a potential novel therapeutic strategy in neuroinflammatory diseases.
|
Neurochemical research
| 2,015 | 11 | 2 | 6 |
26,258,776 |
A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).
|
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.
|
International journal of molecular sciences
| 2,015 | 8 | 2 | 12 |
25,086,773 |
QSAR design of triazolopyridine mGlu2 receptor positive allosteric modulators.
|
Two QSAR approaches were applied to assist the design and to prioritise the synthesis of new active mGlu2 receptor positive allosteric modulators (PAMs). With the aim to explore a particular point of substitution the models successfully prioritised molecules originating from chemistry ideas and a large virtual library. The two methods, 3D topomer CoMFA and support vector machines with 2D ECFP6 fingerprints, delivered good correlation and success in this prospective application. Fourteen molecules with different substituent decoration were identified by the in silico models and synthesised. They were found to be highly active and their mGlu2 receptor PAM activity (pEC50) was predicted within 0.3 and 0.4log units of error with the two methods. The value of the molecules and the models for the future of the project is discussed.
|
Journal of molecular graphics & modelling
| 2,014 | 9 | 1 | 16 |
31,692,680 |
Alpha synuclein in hematopoiesis and immunity.
|
Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular deposition of Lewy bodies in the substantia nigra (SN), which can cause dopaminergic neuronal death, is the hallmark of this syndrome. α-synuclein (syn) is a small protein expressed mainly in neurons but can also be found in a number of tissues. It can be present as a soluble monomer under normal physiological conditions, but can be toxic in its oligomeric or fibrillary forms. Most of the available literature has focused on the effects of α-syn pathology in the mechanisms leading to PD. However, the normal functions of α-syn still remain to be fully elucidated. Notably, α-syn in the hematopoietic system seems to mediate important functions as indicated by anemia and incomplete cell maturation when this protein is absent. This review will summarize basic genetic and structural findings, and critical information that suggests an essential role of α-syn in the development and activation of the hematopoietic system and immunity.
|
Heliyon
| 2,019 | 10 | 1 | 44 |
25,680,364 |
Development and characterisation of novel fentanyl-delta opioid receptor antagonist based bivalent ligands.
|
Opioid tolerance is a limiting factor in chronic pain. Delta opioid peptide (DOP)(δ) receptor antagonism has been shown to reduce tolerance. Here, the common clinical mu opioid peptide (MOP)(µ) receptor agonist fentanyl has been linked to the DOP antagonist Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydrisoquinoline-3-carboxylic acid) to create new bivalent compounds.
|
British journal of anaesthesia
| 2,015 | 4 | 0 | 5 |
27,325,209 |
Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?
|
Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.
|
Trends in neurosciences
| 2,016 | 8 | 21 | 206 |
23,931,992 |
The need for research maps to navigate published work and inform experiment planning.
|
The increasing volume, complexity, and interconnectedness of published studies in neuroscience make it difficult to determine what is known, what is uncertain, and how to contribute effectively to one's field. There is a pressing need to develop automated strategies to help researchers navigate the vastness of the published record. Simplified, interactive, and unbiased representations of previous findings (i.e., research maps) would be invaluable in preparing research surveys, in guiding experiment planning, and in evaluating research plans and contributions. Principles normally used in weighing research findings, including reproducibility and convergence, could be automated and incorporated into research maps. Here, we discuss a series of recent advances that are bringing us closer than ever to being able to derive systematic, comprehensive, but also interactive and user-friendly research maps. These maps could revolutionize the way we review the literature, plan experiments, and fund and publish science.
|
Neuron
| 2,013 | 8 | 1 | 7 |
33,770,610 |
Psychological status after insulo-opercular resection in patients with epilepsy: Depression, anxiety, and quality of life.
|
Insular epilepsy is increasingly recognized in epilepsy surgery centers. Recent studies suggest that resection of an epileptogenic zone that involves the insula as a treatment for drug-resistant seizures is associated with good outcomes in terms of seizure control. However, despite the existing evidence of a role of the insula in emotions and affective information processing, the long-term psychological outcome of patients undergoing these surgeries remain poorly documented. A group of 27 adults (18 women) who underwent an insulo-opercular resection (in combination with a part of the temporal lobe in 10, and of the frontal lobe in 5) as part of epilepsy surgery at our center between 2004 and 2019 completed psychometric questionnaires to assess depression (Beck Depression Inventory - 2nd edition; BDI-II), anxiety (State-Trait Anxiety Inventory, Trait Version; STAI-T), and quality of life (Patient Weighted Quality of Life In Epilepsy; QOLIE-10-P). Scores were compared to those of patients who had standard temporal lobe epilepsy (TLE) surgery with similar socio-demographic and disease characteristics. Seizure control after insular epilepsy surgery was comparable to that observed after TLE surgery, with a majority of patients reporting being seizure free (insular: 63.0%; temporal: 63.2%) or having rare disabling seizures (insular: 7.4%; temporal: 18.4%) at the time of questionnaire completion. Statistical comparisons revealed no significant group difference on scores of depression, anxiety, or quality of life. Hemisphere or extent of insular resection had no significant effect on the studied variables. In the total sample, employment status and seizure control, but not location of surgery, significantly predicted quality of life. Self-reported long-term psychological status after insulo-opercular resection as part of epilepsy surgery thus appears to be similar to that observed after TLE surgery, which is commonly performed in epilepsy surgery centers.
|
Epilepsy & behavior : E&B
| 2,021 | 5 | 0 | 5 |
24,780,955 |
Immediate effect of spinal magnetic stimulation on camptocormia in Parkinson's disease.
|
Spinal cord stimulation is a potential therapeutic option for the treatment of Parkinson's disease (PD)-associated symptoms. Repetitive trans-spinal magnetic stimulation (rTSMS) is a non-invasive and safe alternative for stimulation of spinal pathways that has not been studied for therapeutic efficacy in PD. We assessed the benefits of rTSMS on camptocormia, an often treatment-resistant postural abnormality observed in PD patients.
|
Journal of neurology, neurosurgery, and psychiatry
| 2,014 | 11 | 7 | 18 |
30,937,695 |
Exploring physicians, nurses and ward-based pharmacists working relationships in a Swedish inpatient setting: a mixed methods study.
|
Background In Sweden there has been limited work investigating the integration and nature of collaborative relationships between pharmacists and other healthcare practitioners. Objective To explore the working relationships of physicians, nurses and ward-based pharmacists in a rural hospital after the introduction of a clinical pharmacy service. Setting General medical ward in a rural hospital in northern Sweden. Method Mixed methods involving face-to-face semi-structured interviews with nurses, physicians and pharmacists, and a physician survey using the Physician-Pharmacist Collaboration Index to measure the extent of physician-reported collaborative working relationships. Main outcome measure Perceptions about collaborative working relationships between physician, nurses and pharmacists. Results All physicians (n = 9) who interacted with the clinical pharmacists completed the survey. The mean total score was 78.6 ± 4.7, total 92 (higher scores represent a more advanced relationship). Mean domain scores were highest for relationship initiation (13.0 ± 1.3, total 15), and trustworthiness (38.9 ± 3.4, total 42), followed by role specification (26.3 ± 2.6, total 30). The interviews (with nurses and physicians), showed how communication, collaboration and joint knowledge-exchange in the intervention changed and developed over time. Conclusion This study provides new insights into collaborative working relationships from the perspectives of physicians and nurses. The Physician-Pharmacist Collaboration Index scores suggest that physicians felt that clinical pharmacists were active in providing patient care; could be trusted to follow up on recommendations; and were credible. The interviews suggest that the team-based intervention provided good conditions for creating new ways to work to achieve commitment to professional working relationships.
|
International journal of clinical pharmacy
| 2,019 | 6 | 2 | 20 |
19,186,032 |
Interaction of dopamine D1 with NMDA NR1 receptors in rat prefrontal cortex.
|
Despite the tremendous importance of D1 and NMDA receptors to cognition (working memory, executive functions) and synaptic plasticity in the prefrontal cortex (PFC), little is known about the molecular mechanisms underlying D1-NMDA receptors interactions in this brain area. Here, we show that D1 receptors and the NMDA receptor co-localize in single pyramidal neurons and interneurons in adult rat PFC. NR1 and NR2A expression are found in different neuronal types. Conversely, D1 receptors are predominantly localized in pyramidal-like cells and parvalbumin positive cells. NR1 co-immunoprecipitates with D1 receptor in adult medial PFC. In prefrontal primary cultures, NMDA does not affect the D1 receptor dependent-cAMP production. In contrast, activation of D1 receptor potentiates the NMDA mediated increase in cytosolic Ca2+, an effect that was blocked by a PKA inhibitor. We conclude that D1 receptor potentiates the NMDA-Ca2+ signal by a PKA-dependent mechanism.
|
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
| 2,009 | 4 | 6 | 23 |
22,079,491 |
Regional specific alterations in brain acetylcholinesterase activity after repeated blast exposures in mice.
|
Acetylcholinesterase (AChE) which catalyzes the hydrolysis of the neurotransmitter acetylcholine has been recognized as one of the major regulators of stress responses after traumatic brain injury (TBI). Repeated blast exposure induces TBI (blast TBI) with a variable neuropathology at different brain regions. Since AChE inhibitors are being used as a line of treatment for TBI, we sought to determine the time course of AChE activity in the blood and different brain regions after repeated blast exposures using modified Ellman assay. Our data showed that repeated blast exposures significantly reduced AChE activity in the whole-blood and erythrocytes by 3-6h, while plasma AChE activity was significantly increased by 3h post-blast. In the brain, significant increase in AChE activity was observed at 6h in the frontal cortex, while hind cortex and hippocampus showed a significant decrease at 6h post-blast, which returned to normal levels by 7 days. AChE activity in the cerebellum and mid brain showed a decrease at 6h, followed by significant increase at 3 days and that was decreased significantly at 14 days post-blast. Medulla region showed decreased AChE activity at 24h post-blast, which was significantly increased at 14 days. These results suggest that there are brain regional and time-related changes in AChE activity after tightly coupled repeated blast exposures in mice. In summary, acute and chronic regional specific changes in the AChE activity after repeated blast exposures warrant systematic evaluation of the possibility of AChE inhibitor therapeutics against blast TBI.
|
Neuroscience letters
| 2,012 | 1 | 2 | 9 |
29,728,693 |
Applications and efficiencies of the first cat 63K DNA array.
|
The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.
|
Scientific reports
| 2,018 | 5 | 2 | 36 |
26,243,231 |
Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial.
|
The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide.
|
Stroke
| 2,015 | 9 | 3 | 25 |
26,391,125 |
Differential motor and prefrontal cerebello-cortical network development: Evidence from multimodal neuroimaging.
|
While our understanding of cerebellar structural development through adolescence and young adulthood has expanded, we still lack knowledge of the developmental patterns of cerebellar networks during this critical portion of the lifespan. Volume in lateral posterior cerebellar regions associated with cognition and the prefrontal cortex develops more slowly, reaching their peak volume in adulthood, particularly as compared to motor Lobule V. We predicted that resting state functional connectivity of the lateral posterior regions would show a similar pattern of development during adolescence and young adulthood. That is, we expected to see changes over time in Crus I and Crus II connectivity with the cortex, but no changes in Lobule V connectivity. Additionally, we were interested in how structural connectivity changes in cerebello-thalamo-cortical white matter are related to changes in functional connectivity. A sample of 23 individuals between 12 and 21years old underwent neuroimaging scans at baseline and 12months later. Functional networks of Crus I and Crus II showed significant connectivity decreases over 12months, though there were no differences in Lobule V. Furthermore, these functional connectivity changes were correlated with increases in white matter structural integrity in the corresponding cerebello-thalamo-cortical white matter tract. We suggest that these functional network changes are due to both later pruning in the prefrontal cortex as well as further development of the white matter tracts linking these brain regions.
|
NeuroImage
| 2,016 | 1 | 2 | 30 |
27,401,224 |
Prognostic factors for survival in patients with amyotrophic lateral sclerosis: analysis of a multi-centre clinical trial.
|
Information regarding factors influencing prognosis and quality of life (QoL) in patients with amyotrophic lateral sclerosis (ALS) is useful for clinicians and also for patients and their carers. The aims of this study are to identify prognostic factors for survival in ALS and to determine the physical factors influencing QoL. This study is a retrospective analysis of a cohort of 512 patients who participated in a phase II/III clinical trial of olesoxime. Cox multivariate regression analysis found older age, bulbar onset disease, low baseline forced vital capacity, low baseline manual muscle test (MMT) scores and a shorter diagnostic delay to be independently associated with poor survival outcome. Physical factors shown to have the strongest correlation with poor QoL were low weight and a reduced ability to climb stairs. Therapeutic interventions including gastrostomy and non-invasive ventilation had no positive impact on QoL in this cohort. The prognostic factors for survival identified here are consistent with other studies of ALS patients, with the additional identification of baseline MMT score as another predictor of prognosis. Furthermore, the correlation between both weight and poor lower limb function with QoL is novel and underlines the importance of careful nutritional management in this hypercatabolic condition.
|
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
| 2,016 | 10 | 1 | 8 |
30,741,601 |
Human NOC3 is essential for DNA replication licensing in human cells.
|
Noc3p (Nucleolar Complex-associated protein) is an essential protein in budding yeast DNA replication licensing. Noc3p mediates the loading of Cdc6p and MCM proteins onto replication origins during the M-to-G
|
Cell cycle (Georgetown, Tex.)
| 2,019 | 3 | 0 | 4 |
20,577,882 |
Phonotaxis to male's calls embedded within a chorus by female gray treefrogs, Hyla versicolor.
|
During the reproductive season, male Hyla versicolor produce advertisement calls to attract females. Females exhibit phonotaxis and approach the individual callers, resulting in amplexus. For frogs that call from dense choruses, the extent to which and the range from which a male's advertisement call within a chorus can be heard by a receptive female leading to phonotaxis is unclear. We investigated females' responses to natural choruses in the field and found that they were attracted and showed directed orientation to breeding choruses at distances up to 100 m. To assess the role of acoustic cues in the directed orientation, we conducted acoustic playback experiments in the laboratory using conspecific call and noise as stimuli, as well as chorus sounds (that contained calls from a focal male) recorded at various distances, all played at naturalistic intensities. Using two response metrics (females' normalized response times and their phonotaxis trajectories) we found that, unlike the field experiments, females oriented and were attracted to chorus sounds from 1 to 32 m only, but not from >32 m, or to band-limited noise. Possible reasons for the observed difference in phonotaxis behavior in the two experimental conditions were discussed.
|
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology
| 2,010 | 8 | 0 | 11 |
32,516,938 |
Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models.
|
Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.
|
Cells
| 2,020 | 6 | 0 | 4 |
33,675,270 |
Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.
|
Niemann-Pick disease Types A and B (NPA/B) are autosomal recessive disorders caused by variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. This study aimed to describe and characterize a cohort of 118 patients diagnosed with NPA/B based on clinical, biochemical, and molecular findings, and to identify sound correlations between laboratory findings and clinical presentations. Decreased peripheral leukocyte acid sphingomyelinase activity levels and increased plasma 7-ketocholesterol levels were significantly correlated with disease onset and severity of the clinical course. We identified 92 different sequence SMPD1 variants, including 41 novel variants, in 118 NPA/B patients (19 NPA, 24 intermediate type, 75 NPB). The most prevalent mutation was p.Arg602His, which accounted for 9.3% of the alleles. Patients homozygous for p.Arg602His or p.Asn522Ser showed a late-onset form of the NPB phenotype. The homozygous SMPD1 variant p.Tyr500His correlated with the early-onset NPB clinical form. Additionally, homozygous variants p.His284SerfsX18, p.Phe465Ser, and p.Ser486Arg were associated with the neuronopathic NPA clinical form. The homozygous variant p.Arg3AlafsX74 was associated with the intermediate clinical form. Our study contributes to the understanding of the natural history of NPA/B and assists in the development of efficacious treatments for patients afflicted with this devastating lysosomal storage disorder.
|
Human mutation
| 2,021 | 5 | 3 | 24 |
29,024,786 |
Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent and Non-Dependent Rats.
|
Repeated use of opioids can lead to the development of analgesic tolerance and dependence. Additionally, chronic opioid exposure can cause a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may drive continued or escalated use of opioids to manage worsening pain symptoms. Opioid-induced hyperalgesia has traditionally been measured in rodents via reflex-based assays, including the von Frey method. To better model the cognitive/motivational dimension of pain in a state of opioid dependence and withdrawal, we employed a recently developed non-reflex-based method for measuring pain avoidance-like behavior in animals (mechanical conflict avoidance test). Adult male Wistar rats were administered an escalating dose regimen of morphine (opioid-dependent group) or repeated saline (control group). Morphine-dependent rats exhibited significantly greater avoidance of noxious stimuli during withdrawal. We next investigated individual relationships between pain avoidance-like behavior and alterations in protein phosphorylation in central motivation-related brain areas. We discovered that pain avoidance-like behavior was significantly correlated with alterations in phosphorylation status of protein kinases (ERK, CaMKII), transcription factors (CREB), presynaptic markers of neurotransmitter release (Synapsin), and the rate-limiting enzyme for dopamine synthesis (TH) across specific brain regions. Our findings suggest that alterations in phosphorylation events in specific brain centers may support cognitive/motivational responses to avoid pain.
|
Neuroscience
| 2,017 | 12 | 2 | 20 |
28,685,178 |
Time-based event expectancies in children with Autism spectrum disorder.
|
Here, we studied the time-based event expectancies in children with Autism spectrum disorder. Nine children with Autism spectrum disorders and ten (6-11 years) typically developing children participated. In a choice-response task with two different pre-target intervals, participants had to indicate the left or right direction of a target stimulus. The target was predicted by the duration of the pre-target interval with 80% validity. We found that, in children with Autism spectrum disorder, in contrast to typically developing children, the formation of time-based event expectancies was restricted to the relatively longer pre-target interval. This pattern is rather typical for healthy young adults. These findings indicate that children with Autism spectrum disorder are able to form time-based event expectancies, and that, similar to healthy young adults, longer pre-target intervals enable them to make more optimal temporal predictions.
|
Experimental brain research
| 2,017 | 9 | 0 | 7 |
28,981,614 |
Neurotensin Broadly Recruits Inhibition via White Matter Neurons in the Mouse Cerebral Cortex: Synaptic Mechanisms for Decorrelation.
|
The neuropeptide, neurotensin (NT), inhibits UP state generation in the cerebral cortex and temporally restricts the response to thalamic input, likely by a generalized increase in inhibition. To investigate the cellular and circuit substrate(s) for how a neuropeptide can shift the balance between cortical excitation and inhibition, we performed whole-cell recordings on slice preparations from mice expressing enhanced green fluorescent protein under control of the promoter for the homeobox gene, lhx6 (lhx6-EGFP mice). These mice identify the 2 largest classes of cortical interneurons; FS and low-threshold-spiking inhibitory neurons. In the presence of NT, both types of lhx6-EGFP neurons were excited through a direct, Na+-dependent depolarization, and through an increase in synaptic excitation. Paired recordings identified cortical white matter (WM) neurons as a source of this excitatory input, which was strengthened in the presence of NT. NT-driven increased synaptic input caused a functional decorrelation of gap junction transmission between lhx6-EGFP neuron pairs. Finally, the synaptic transmission between pyramidal cells and lhx6-EGFP neurons was modulated by addition of NT in favor of stronger inhibition and weaker excitation. These findings demonstrate the existence and functional consequences of an intracortical WM neuron projection, and suggest mechanisms underlying NT-induced promotion of wakefulness.
|
Cerebral cortex (New York, N.Y. : 1991)
| 2,018 | 8 | 2 | 4 |
22,539,857 |
Cervical spinal erythropoietin induces phrenic motor facilitation via extracellular signal-regulated protein kinase and Akt signaling.
|
Erythropoietin (EPO) is typically known for its role in erythropoiesis but is also a potent neurotrophic/neuroprotective factor for spinal motor neurons. Another trophic factor regulated by hypoxia-inducible factor-1, vascular endothelial growth factor (VEGF), signals via ERK and Akt activation to elicit long-lasting phrenic motor facilitation (pMF). Because EPO also signals via ERK and Akt activation, we tested the hypothesis that EPO elicits similar pMF. Using retrograde labeling and immunohistochemical techniques, we demonstrate in adult, male, Sprague Dawley rats that EPO and its receptor, EPO-R, are expressed in identified phrenic motor neurons. Intrathecal EPO at C4 elicits long-lasting pMF; integrated phrenic nerve burst amplitude increased >90 min after injection (63 ± 12% baseline 90 min after injection; p < 0.001). EPO increased phosphorylation (and presumed activation) of ERK (1.6-fold vs controls; p < 0.05) in phrenic motor neurons; EPO also increased pAkt (1.6-fold vs controls; p < 0.05). EPO-induced pMF was abolished by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one], demonstrating that ERK MAP kinases and Akt are both required for EPO-induced pMF. Pretreatment with U0126 and LY294002 decreased both pERK and pAkt in phrenic motor neurons (p < 0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Because EPO expression is hypoxia sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,012 | 4 | 4 | 28 |
27,716,964 |
Immediate Neural Plasticity Involving Reaction Time in a Saccadic Eye Movement Task is Intact in Children With Fetal Alcohol Spectrum Disorder.
|
Saccades are rapid eye movements that bring an image of interest onto the retina. Previous research has found that in healthy individuals performing eye movement tasks, the location of a previous visual target can influence performance of the saccade on the next trial. This rapid behavioral adaptation represents a form of immediate neural plasticity within the saccadic circuitry. Our studies have shown that children with fetal alcohol spectrum disorder (FASD) are impaired on multiple saccade measures. We therefore investigated these previous trial effects in typically developing children and children with FASD to measure sensory neural plasticity and how these effects vary with age and pathology.
|
Alcoholism, clinical and experimental research
| 2,016 | 11 | 0 | 1 |
22,083,597 |
Influences on blockade by t-butylbicyclo-phosphoro-thionate of GABA(A) receptor spontaneous gating, agonist activation and desensitization.
|
Picrotoxin and t-butylbicyclophosphorothionate (TBPS) are GABA(A) receptor (GABA(A)R) open channel blockers. However, picrotoxin displaceable [(35)S]TBPS binding to α1β2γ2 GABA(A)Rs occurs in the absence of GABA, suggesting that access to the binding site is independent of activation. Alternatively, spontaneous gating may provide access to the channel. In the absence of episodic GABA application, picrotoxin and TBPS blocked (by 91 ± 3% and 85 ± 5%, respectively) GABA-evoked currents mediated by α1β2γ2 receptors. We used two approaches to inhibit spontaneous GABA(A)R gating, bicuculline, which inhibits spontaneous current in the absence of exogenous agonist and the α1(K278M) mutant subunit. Whole-cell patch-clamp recordings demonstrated that α1(K278M)β2γ2 receptors have negligible spontaneous gating. Application of bicuculline to α1β2γ2 receptors in the absence of exogenous GABA caused a 35% reduction of current blockade by TBPS and reduced [(35)S]TBPS binding by 25%. Consistent with this, in the absence of exogenous GABA, α1(K278M)β2γ2 receptors exhibited reduced blockade by TBPS current compared to wild-type receptors. These data suggest that a decrease in spontaneous gating reduces accessibility of TBPS to its binding site. GABA application during picrotoxin or TBPS administration enhanced α1β2γ2 receptor blockade (to 98% in both cases). The GABA-dependent component of TBPS blockade accounts for the stimulation of [(35)S]TBPS binding to α1β2γ2 receptors seen with GABA (1 μm) application. Moreover, application of GABA at concentrations that cause significant steady-state desensitization reduced [(35)S]TBPS binding. The α1(K278M) subunit slowed desensitization kinetics and increased the rate of deactivation of GABA-evoked currents. Furthermore, there was a marked increase in the GABA EC(50) for desensitization of α1(K278M)β2γ2 receptors associated with a large increase in the GABA-dependent stimulation of [(35)S]TBPS binding. These data establish a relationship between GABA(A)R function and the three phases of [(35)S]TBPS binding seen in the absence and the presence of GABA.
|
The Journal of physiology
| 2,012 | 1 | 1 | 7 |
25,504,741 |
Involvement of the endocannabinoid system in attentional modulation of nociceptive behaviour in rats.
|
Distraction is used clinically to relieve and manage pain. It is hypothesized that pain demands attention and that exposure to another attention-demanding stimulus causes withdrawal of attention away from painful stimuli, thereby reducing perceived pain. We have recently developed a rat model that provides an opportunity to investigate the neurobiological mechanisms mediating distraction-induced analgesia, as these mechanisms are, at present, poorly understood. Given the well-described role of the endogenous cannabinoid (endocannabinoid; EC) system in the modulation of pain and attentional processing, the present study investigated its role in distraction-induced antinociception in rats.
|
European journal of pain (London, England)
| 2,015 | 9 | 0 | 6 |
23,011,918 |
Increased expression of the glucose-responsive gene, RCAN1, causes hypoinsulinemia, β-cell dysfunction, and diabetes.
|
RCAN1 is a chromosome 21 gene that controls secretion in endocrine cells, regulates mitochondrial function, and is sensitive to oxidative stress. Regulator of calcineurin 1 (RCAN1) is also an endogenous inhibitor of the protein phosphatase calcineurin, the inhibition of which leads to hypoinsulinemia and diabetes in humans and mice. However, the presence or the role of RCAN1 in insulin-secreting β-cells and its potential role in the pathogenesis of diabetes is unknown. Hence, the aim of this study is to investigate the presence of RCAN1 in β-cells and identify its role in β-cell function. RCAN1 is expressed in mouse islets and in the cytosol of pancreatic β-cells. We find RCAN1 is a glucose-responsive gene with a 1.5-fold increase in expression observed in pancreatic islets in response to chronic hyperglycemia. The overexpression of the human RCAN1.1 isoform in mice under the regulation of its endogenous promoter causes diabetes, age-associated hyperglycemia, reduced glucose tolerance, hypoinsulinemia, loss of β-cells, reduced β-cell insulin secretion, aberrant mitochondrial reactive oxygen species production, and the down-regulation of key β-cell genes. Our data therefore identifies a novel molecular link between the overexpression of RCAN1 and β-cell dysfunction. The glucose-responsive nature of RCAN1 provides a potential mechanism of action associated with the β-cell dysfunction observed in diabetes.
|
Endocrinology
| 2,012 | 11 | 0 | 14 |
32,173,153 |
Carbon fiber reinforced vs titanium implants for fixation in spinal metastases: A comparative clinical study about safety and effectiveness of the new "carbon-strategy".
|
In spinal oncology traditional titanium implants could significantly impair evaluation of postoperative imaging because of artifacts, potentially affecting proper planning and execution of radiotherapy and adequate radiological follow-up to rule out progression of the disease. This is why carbon fiber reinforced (CFR)-PEEK implants have been developed for spinal fixation. The advantages of this system include fewer artifacts on imaging, potentially improving the execution and quality of radiotherapy, with also a reduced scattering effect to neighboring tissues. A comparative clinical and radiological study between new CFR-PEEK and standard titanium implants is described. Data recorded for each case included patient demographics, clinical, radiological and surgical data, intra- and postoperative complications, follow-up information. The goal of this study was to verify the safety and effectiveness of CFR-PEEK devices compared to standard titanium implants. A total number of 78 patients were reviewed. 36 patients underwent CFR-PEEK fixation, while titanium implants were used for 42 patients. Functional recovery was obtained in both groups and registered at last follow-up in terms of axial pain and neurological status. No significative differences were found between the two groups in terms of post-operative clinical complications and hardware-related complications. CFR-PEEK implants constitute a feasible and effective way to restore stability in metastatic spine tumors. This study found a non inferior favorable profile in terms of intraoperative and postoperative complications and functional recovery, compared to titanium. Further prospective studies are needed to clarify the potential oncological advantage of their radiolucency.
|
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
| 2,020 | 5 | 7 | 48 |
27,698,428 |
Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.
|
Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined a continuum of poor to highly functional electrophysiological states of differentiated neurons. The strong correlations between action potentials, synaptic activity, dendritic complexity and gene expression highlight the importance of methods for isolating functionally comparable neurons for in vitro investigations of brain disorders. Although whole-cell electrophysiology is the gold standard for functional evaluation, it often lacks the scalability required for disease modeling studies. Here, we demonstrate a multimodal machine-learning strategy to identify new molecular features that predict the physiological states of single neurons, independently of the time spent in vitro. As further proof of concept, we selected one of the potential neurophysiological biomarkers identified in this study-GDAP1L1-to isolate highly functional live human neurons in vitro.
|
Molecular psychiatry
| 2,016 | 11 | 4 | 86 |
28,545,908 |
Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods.
|
Recent interest in the lasting effects of early-life stress has expanded to include effects on cognitive performance. An increase in circulating glucocorticoids is induced by stress exposure and glucocorticoid effects on the hippocampus likely underlie many of the cognitive consequences. Here we review studies showing that corticosterone administered to young rats at the conclusion of the stress-hyporesponsiveness period affects later performance in hippocampally-mediated trace eyeblink conditioning. The nature and even direction of these effects varies with the elevation patterns (level, duration, temporal fluctuation) achieved by different administration methods. We present new time course data indicating that constant glucocorticoid elevations generally corresponded with hippocampus-mediated learning deficits, whereas acute, cyclical elevations corresponded with improved initial acquisition. Sensitivity was greater for males than for females. Further, changes in hippocampal neurogenesis paralleled some but not all effects. The findings demonstrate that specific patterns of glucocorticoid elevation produced by different drug administration procedures can have markedly different, sex-specific consequences on basic cognitive performance and underlying hippocampal physiology. Implications of these findings for glucocorticoid medications prescribed in childhood are discussed.
|
Neurobiology of learning and memory
| 2,017 | 9 | 0 | 5 |
25,873,042 |
The dopamine theory of addiction: 40 years of highs and lows.
|
For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.
|
Nature reviews. Neuroscience
| 2,015 | 5 | 30 | 254 |
28,744,955 |
Cortical connectivity modulation during sleep onset: A study via graph theory on EEG data.
|
Sleep onset is characterized by a specific and orchestrated pattern of frequency and topographical EEG changes. Conventional power analyses of electroencephalographic (EEG) and computational assessments of network dynamics have described an earlier synchronization of the centrofrontal areas rhythms and a spread of synchronizing signals from associative prefrontal to posterior areas. Here, we assess how "small world" characteristics of the brain networks, as reflected in the EEG rhythms, are modified in the wakefulness-sleep transition comparing the pre- and post-sleep onset epochs. The results show that sleep onset is characterized by a less ordered brain network (as reflected by the higher value of small world) in the sigma band for the frontal lobes indicating stronger connectivity, and a more ordered brain network in the low frequency delta and theta bands indicating disconnection on the remaining brain areas. Our results depict the timing and topography of the specific mechanisms for the maintenance of functional connectivity of frontal brain regions at the sleep onset, also providing a possible explanation for the prevalence of the frontal-to-posterior information flow directionality previously observed after sleep onset. Hum Brain Mapp 38:5456-5464, 2017. © 2017 Wiley Periodicals, Inc.
|
Human brain mapping
| 2,017 | 11 | 2 | 38 |
25,350,774 |
Persistent reduction of hippocampal glutamine synthetase expression after status epilepticus in immature rats.
|
Mesiotemporal sclerosis (MTS), the most frequent form of drug-resistant temporal lobe epilepsy, often develops after an initial precipitating injury affecting the immature brain. To analyse early processes in epileptogenesis we used the juvenile pilocarpine model to study status epilepticus (SE)-induced changes in expression of key components in the glutamate-glutamine cycle, known to be affected in MTS patients. SE was induced by Li(+) /pilocarpine injection in 21-day-old rats. At 2-19 weeks after SE hippocampal protein expression was analysed by immunohistochemistry and neuron damage by FluoroJade staining. Spontaneous seizures occurred in at least 44% of animals 15-18 weeks after SE. As expected in this model, we did not observe loss of principal hippocampal neurons. Neuron damage was most pronounced in the hilus, where we also detected progressive loss of parvalbumin-positive GABAergic interneurons. Hilar neuron loss (or end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity from 2 (-15%) to 19 weeks (-33.5%) after SE. Immunoreactivity for excitatory amino-acid transporters, vesicular glutamate transporter 1 and glial fibrillary acidic protein was unaffected. Our data show that SE elicited in 21-day-old rats induces a progressive reduction in hilar GS expression without affecting other key components of the glutamate-glutamine cycle. Reduced expression of glial enzyme GS was first detected 2 weeks after SE, and thus clearly before spontaneous recurrent seizures occurred. These results support the hypothesis that reduced GS expression is an early event in the development of hippocampal sclerosis in MTS patients and emphasize the importance of astrocytes in early epileptogenesis.
|
The European journal of neuroscience
| 2,014 | 12 | 0 | 8 |
31,707,193 |
Functional reorganization during the recovery of contralesional target selection deficits after prefrontal cortex lesions in macaque monkeys.
|
Visual extinction has been characterized by the failure to respond to a visual stimulus in the contralesional hemifield when presented simultaneously with an ipsilesional stimulus (Corbetta and Shulman, 2011). Unilateral damage to the macaque frontoparietal cortex commonly leads to deficits in contralesional target selection that resemble visual extinction. Recently, we showed that macaque monkeys with unilateral lesions in the caudal prefrontal cortex (PFC) exhibited contralesional target selection deficits that recovered over 2-4 months (Adam et al., 2019). Here, we investigated the longitudinal changes in functional connectivity (FC) of the frontoparietal network after a small or large right caudal PFC lesion in four macaque monkeys. We collected ultra-high field resting-state fMRI at 7-T before the lesion and at weeks 1-16 post-lesion and compared the functional data with behavioural performance on a free-choice saccade task. We found that the pattern of frontoparietal network FC changes depended on lesion size, such that the recovery of contralesional extinction was associated with an initial increase in network FC that returned to baseline in the two small lesion monkeys, whereas FC continued to increase throughout recovery in the two monkeys with a larger lesion. We also found that the FC between contralesional dorsolateral PFC and ipsilesional parietal cortex correlated with behavioural recovery and that the contralesional dorsolateral PFC showed increasing degree centrality with the frontoparietal network. These findings suggest that both the contralesional and ipsilesional hemispheres play an important role in the recovery of function. Importantly, optimal compensation after large PFC lesions may require greater recruitment of distant and intact areas of the frontoparietal network, whereas recovery from smaller lesions was supported by a normalization of the functional network.
|
NeuroImage
| 2,020 | 2 | 1 | 14 |
27,355,516 |
Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.
|
Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.
|
Small GTPases
| 2,017 | 4 | 0 | 3 |
24,388,038 |
A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action.
|
Recent research has seen low-dose ketamine emerge as a novel, rapid-acting antidepressant. Ketamine, an N-methy-d-aspartate (NMDA) receptor antagonist, leads to effects on the glutamatergic system and abnormalities in this neurotransmittor system are present in depression. This article aims to (1) review the clinical literature on low-dose ketamine as a rapid-acting antidepressant in affective disorders, (2) provide a critical overview of the limitations of ketamine and research attempts to overcome these (3) discuss the proposed mechanisms of action of ketamine and (4) point towards future research directions.
|
Journal of affective disorders
| 2,014 | 3 | 18 | 113 |
31,914,896 |
Neuropathic Pain: Mechanism-Based Therapeutics.
|
Neuropathic pain (NeP) can result from sources as varied as nerve compression, channelopathies, autoimmune disease, and incision. By identifying the neurobiological changes that underlie the pain state, it will be clinically possible to exploit mechanism-based therapeutics for maximum analgesic effect as diagnostic accuracy is optimized. Obtaining sufficient knowledge regarding the neuroadaptive alterations that occur in a particular NeP state will result in improved patient analgesia and a mechanism-based, as opposed to a disease-based, therapeutic approach to facilitate target identification. This will rely on comprehensive disease pathology insight; our knowledge is vastly improving due to continued forward and back translational preclinical and clinical research efforts. Here we discuss the clinical aspects of neuropathy and currently used drugs whose mechanisms of action are outlined alongside their clinical use. Finally, we consider sensory phenotypes, patient clusters, and predicting the efficacy of an analgesic for neuropathy.
|
Annual review of pharmacology and toxicology
| 2,020 | 1 | 15 | 166 |
25,563,647 |
Ethanol and normobaric oxygen: novel approach in modulating pyruvate dehydrogenase complex after severe transient and permanent ischemic stroke.
|
Ischemic stroke induces metabolic disarray. A central regulatory site, pyruvate dehydrogeanse complex (PDHC) sits at the cross-roads of 2 fundamental metabolic pathways: aerobic and anaerobic. In this study, we combined ethanol (EtOH) and normobaric oxygen (NBO) to develop a novel treatment to modulate PDHC and its regulatory proteins, namely pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase, leading to improved metabolism and reduced oxidative damage.
|
Stroke
| 2,015 | 2 | 6 | 19 |
23,843,519 |
TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway.
|
Toll-like receptors (TLRs) recognize both pathogen- and danger-associated molecular patterns and induce innate immune responses. Some TLRs are expressed in neurons and regulate neurodevelopment and neurodegeneration. However, the downstream signaling pathways and effectors for TLRs in neurons are still controversial. In this report, we provide evidence that TLR7 negatively regulates dendrite growth through the canonical myeloid differentiation primary response gene 88 (Myd88)-c-Fos-interleukin (IL)-6 pathway. Although both TLR7 and TLR8 recognize single-stranded RNA (ssRNA), the results of quantitative reverse transcription-PCR suggested that TLR7 is the major TLR recognizing ssRNA in brains. In both in vitro cultures and in utero electroporation experiments, manipulation of TLR7 expression levels was sufficient to alter neuronal morphology, indicating the presence of intrinsic TLR7 ligands. Besides, the RNase A treatment that removed ssRNA in cultures promoted dendrite growth. We also found that the addition of ssRNA and synthetic TLR7 agonists CL075 and loxoribine, but not R837 (imiquimod), to cultured neurons specifically restricted dendrite growth via TLR7. These results all suggest that TLR7 negatively regulates neuronal differentiation. In cultured neurons, TLR7 activation induced IL-6 and TNF-α expression through Myd88. Using Myd88-, IL-6-, and TNF-α-deficient neurons, we then demonstrated the essential roles of Myd88 and IL-6, but not TNF-α, in the TLR7 pathway to restrict dendrite growth. In addition to neuronal morphology, TLR7 knockout also affects mouse behaviors, because young mutant mice ∼2 weeks of age exhibited noticeably lower exploratory activity in an open field. In conclusion, our study suggests that TLR7 negatively regulates dendrite growth and influences cognition in mice.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,013 | 7 | 3 | 20 |
28,657,428 |
Abnormal functional connectivity of thalamic sub-regions contributes to fatigue in multiple sclerosis.
|
To investigate sub-regional thalamic resting-state (RS) functional connectivity (FC) abnormalities in multiple sclerosis (MS) and their correlation with fatigue and its subcomponents (physical, cognitive, and psychosocial).
|
Multiple sclerosis (Houndmills, Basingstoke, England)
| 2,018 | 8 | 8 | 44 |
31,068,233 |
Place of death and other factors associated with unnatural mortality in patients with serious mental disorders: population-based retrospective cohort study.
|
Patients with serious mental disorders have poorer healthcare outcomes at the end of life and are at greater risk of dying from unnatural causes.AimsTo explore place of death and demographic and clinical correlates of unnatural causes of death in patients with serious mental disorders.
|
BJPsych open
| 2,019 | 3 | 1 | 7 |
27,466,343 |
SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein.
|
Proteolytic generation of amyloidogenic amyloid β (Aβ) fragments from the amyloid precursor protein (APP) significantly contributes to Alzheimer's disease (AD). Although amyloidogenic APP proteolysis can be affected by trafficking through genetically associated AD components such as SORLA, how SORLA functionally interacts with other trafficking components is yet unclear. Here, we report that SNX27, an endosomal trafficking/recycling factor and a negative regulator of the γ-secretase complex, binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels in human cell lines and mouse primary neurons, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances the generation of cell surface APP cleavage products such as soluble alpha-APP C-terminal fragment (CTFα) in a SORLA-dependent manner. SORLA-mediated Aβ reduction is attenuated by downregulation of SNX27. This indicates that an SNX27/SORLA complex functionally interacts to limit APP distribution to amyloidogenic compartments, forming a non-amyloidogenic shunt to promote APP recycling to the cell surface.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,016 | 7 | 3 | 29 |
27,640,074 |
Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.
|
A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis.
|
Neurobiology of aging
| 2,016 | 12 | 1 | 14 |
25,981,149 |
HRS/NSA 2014 survey of atrial fibrillation and stroke: Gaps in knowledge and perspective, opportunities for improvement.
|
The prevalence of atrial fibrillation (AF) is substantial and increasing. Stroke is common in AF and can have devastating consequences. Oral anticoagulants are effective in reducing stroke risk, but are underutilized.
|
Heart rhythm
| 2,015 | 8 | 1 | 14 |
31,015,294 |
Variation in sequence dynamics improves maintenance of stereotyped behavior in an example from bird song.
|
Performing a stereotyped behavior successfully over time requires both maintaining performance quality and adapting efficiently to environmental or physical changes affecting performance. The bird song system is a paradigmatic example of learning a stereotyped behavior and therefore is a good place to study the interaction of these two goals. Through a model of bird song learning, we show how instability in neural representation of stable behavior confers advantages for adaptation and maintenance with minimal cost to performance quality. A precise, temporally sparse sequence from the premotor nucleus HVC is crucial to the performance of song in songbirds. We find that learning in the presence of sequence variations facilitates rapid relearning after shifts in the target song or muscle structure and results in decreased error with neuron loss. This robustness is due to the prevention of the buildup of correlations in the learned connectivity. In the absence of sequence variations, these correlations grow, due to the relatively low dimensionality of the exploratory variation in comparison with the number of plastic synapses. Our results suggest one would expect to see variability in neural systems executing stereotyped behaviors, and this variability is an advantageous feature rather than a challenge to overcome.
|
Proceedings of the National Academy of Sciences of the United States of America
| 2,019 | 5 | 0 | 13 |
33,219,004 |
Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats.
|
Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,021 | 1 | 7 | 17 |
22,964,514 |
Disease mechanisms in MS: phases of disease improvement unrelated to relapses.
|
Natural history of multiple sclerosis includes phases of relapse, remission and insidious progression. New data show that sustained improvements in disease, defined by reductions in EDSS scores, occur independent of relapses almost half as frequently as disease worsening. This finding might facilitate research into the biological processes involved in disease improvement.
|
Nature reviews. Neurology
| 2,012 | 11 | 0 | 1 |
26,661,417 |
Müller glial cell-dependent regeneration of the neural retina: An overview across vertebrate model systems.
|
Retinal dystrophies are a major cause of blindness for which there are currently no curative treatments. Transplantation of stem cell-derived neuronal progenitors to replace lost cells has been widely investigated as a therapeutic option. Another promising strategy would be to trigger self-repair mechanisms in patients, through the recruitment of endogenous cells with stemness properties. Accumulating evidence in the past 15 year0s has revealed that several retinal cell types possess neurogenic potential, thus opening new avenues for regenerative medicine. Among them, Müller glial cells have been shown to be able to undergo a reprogramming process to re-acquire a stem/progenitor state, allowing them to proliferate and generate new neurons for repair following retinal damages. Although Müller cell-dependent spontaneous regeneration is remarkable in some species such as the fish, it is extremely limited and ineffective in mammals. Understanding the cellular events and molecular mechanisms underlying Müller cell activities in species endowed with regenerative capacities could provide knowledge to unlock the restricted potential of their mammalian counterparts. In this context, the present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field. Developmental Dynamics 245:727-738, 2016. © 2015 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc.
|
Developmental dynamics : an official publication of the American Association of Anatomists
| 2,016 | 7 | 8 | 64 |
31,808,207 |
Cerebral small vessel disease with hemorrhagic stroke related to COL4A1 mutation: A case report.
|
Stroke is a major cause of mortality and morbidity with a wide variety of etiological risk factors. Cerebral small vessel disease (SVD) is an important cause of stroke in the young with several hereditary disorders affecting these small blood vessels. Mutations in the COL4A1 gene (COL4A1) have been shown to be associated with a broad range of disorders including hemorrhagic stroke, myopathy, glaucoma and others. We report a rare case of stroke in an intellectually disabled 18-year-old girl with radiological evidence of basal ganglia microbleeds, periventricular white matter signal changes and porencephalic cyst. Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly. At autopsy there were hemorrhagic lesions at multiple sites within the brain. Histology revealed thickened small-caliber vessels which demonstrated disruption and fragmentation of the basement membrane by collagen type IV alpha 1 immunohistochemistry and by electron microscopy. A missense COL4A1 mutation involving glycine residue was detected in the patient. The present case illustrates the clinicopathological spectrum of COL4A1-related cerebral SVD presenting as hemorrhagic stroke in the young with porencephaly, intellectual disability, and Axenfield-Rieger anomaly and thus adds to the clinical heterogeneity of this genetic disorder.
|
Neuropathology : official journal of the Japanese Society of Neuropathology
| 2,020 | 2 | 2 | 11 |
25,850,619 |
Brain rhythms connect impaired inhibition to altered cognition in schizophrenia.
|
In recent years, schizophrenia research has focused on inhibitory interneuron dysfunction at the level of neurobiology and on cognitive impairments at the psychological level. Reviewing both experimental and computational findings, we show how the temporal structure of the activity of neuronal populations, exemplified by brain rhythms, can begin to bridge these levels of complexity. Oscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia.
|
Biological psychiatry
| 2,015 | 6 | 7 | 46 |
30,224,452 |
Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.
|
The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.
|
Proceedings of the National Academy of Sciences of the United States of America
| 2,018 | 10 | 6 | 47 |
9,791,092 |
Vigilance states and body temperature during the circadian cycle in fed and fasted pigeons (Columba livia).
|
Fasting induces nocturnal hypothermia in pigeons. Slow-wave sleep (SWS) and paradoxical sleep (PS) are associated with reduced heat production in pigeons. The possibility that fasting-induced nocturnal hypothermia is related to increased SWS and PS was examined by comparing body temperature (Tb) and vigilance states when pigeons were fed and fasted. The results showed that when Tb is decreasing near the beginning of the dark phase, the percentage of total recording time (%TRT) spent in SWS and PS was elevated in fasting due to increased frequency of episodes and increased duration of PS episodes. When Tb was low during the middle segment of the dark phase, SWS was elevated in fasting due to increased episode duration. However, fasting did not alter PS, which increased in %TRT across the segment due to increased episode frequency. When Tb was rising during the final hours of dark, SWS remained elevated in fasting and %TRT in SWS and PS was relatively high. SWS and PS may promote the fasting pigeon's entry into, and maintenance of, nocturnal hypothermia.
|
The American journal of physiology
| 1,998 | 11 | 0 | 7 |
29,684,289 |
Lonely young adults in modern Britain: findings from an epidemiological cohort study.
|
The aim of this study was to build a detailed, integrative profile of the correlates of young adults' feelings of loneliness, in terms of their current health and functioning and their childhood experiences and circumstances.
|
Psychological medicine
| 2,019 | 1 | 10 | 191 |
18,486,703 |
Outcome of 2 different types of operative techniques practiced for chronic subdural hematoma in Malaysia: an analysis.
|
Traumatic chronic subdural hematomas in Malaysia are increasingly common in young patients after road traffic accidents as well as the elderly who fall at home. Most surgeons in this country manage these pathologies without irrigation, with only a drainage system. This has led to criticism that the recurrence rate might be higher when no irrigation is done and that rates are lower with irrigation and drainage. Thus, a study was done to look into the outcome of TCSH operated with and without irrigation, followed by drainage, to guide the surgeons in Malaysia as to what best could be done for these cases.
|
Surgical neurology
| 2,008 | 6 | 0 | 9 |
24,852,228 |
Corticolimbic connectivity as a possible biomarker for bipolar disorder.
|
Bipolar disorder is a severe, disabling and life-threatening illness, which affects nearly 2% of the general population. The identification of reliable and objective biomarkers may aid early diagnosis and optimize treatment efficacy. Through a careful overview of the neuroimaging studies which investigated the structural, functional, and effective connectivity in bipolar disorder, we explored the role of a disconnected cortico-limbic circuitry in the development and maintenance of the disorder. This review offers perspectives and suggestions for future research, in order to propose the corticolimbic disconnection as a neurobiological underpinning and biomarker for bipolar psychopathology.
|
Expert review of neurotherapeutics
| 2,014 | 6 | 3 | 26 |
32,942,699 |
Emulsifiers Impact Colonic Length in Mice and Emulsifier Restriction is Feasible in People with Crohn's Disease.
|
There is an association between food additive emulsifiers and the prevalence of Crohn's disease. This study aimed to investigate: (i) the effect of different classes of emulsifiers on markers of intestinal inflammation in mice and (ii) the feasibility, nutritional adequacy and symptom impact of restricting all emulsifier classes in Crohn's disease. Mice were exposed to different classes of emulsifiers (carboxymethycellose, polysorbate-80, soy lecithin, gum arabic) in drinking water for 12-weeks, after which markers of inflammation and metabolism were measured. A low emulsifier diet was developed to restrict all classes of emulsifiers and its feasibility measured over 14-days in 20 participants with stable Crohn's disease. Crohn's disease-related symptoms, disease control, body weight and composition, nutrient intake and food-related quality of life (QoL) were measured. All emulsifiers resulted in lower murine colonic length compared with control (mean 9.5 cm (SEM 0.20)), but this only reached significance for polysorbate-80 (8.2 cm (0.34),
|
Nutrients
| 2,020 | 9 | 7 | 39 |
32,636,358 |
Designing m-Health interventions for precision mental health support.
|
Mobile health (m-Health) resources are emerging as a significant tool to overcome mental health support access barriers due to their ability to rapidly reach and provide support to individuals in need of mental health support. m-Health provides an approach to adapt and initiate mental health support at precise moments, when they are most likely to be effective for the individual. However, poor adoption of mental health apps in the real world suggests that new approaches to optimising the quality of m-Health interventions are critically needed in order to realise the potential translational benefits for mental health support. The micro-randomised trial is an experimental approach for optimising and adapting m-Health resources. This trial design provides data to construct and optimise m-Health interventions. The data can be used to inform when and what type of m-Health interventions should be initiated, and thus serve to integrate interventions into daily routines with precision. Here, we illustrate this approach in a case study, review implementation issues that need to be considered while conducting an MRT, and provide a checklist for mental health m-Health intervention developers.
|
Translational psychiatry
| 2,020 | 7 | 3 | 56 |
27,063,782 |
Position Sense in Chronic Pain: Separating Peripheral and Central Mechanisms in Proprioception in Unilateral Limb Pain.
|
Awareness of limb position is derived primarily from muscle spindles and higher-order body representations. Although chronic pain appears to be associated with motor and proprioceptive disturbances, it is not clear if this is due to disturbances in position sense, muscle spindle function, or central representations of the body. This study examined position sense errors, as an indicator of spindle function, in participants with unilateral chronic limb pain. The sample included 15 individuals with upper limb pain, 15 with lower limb pain, and 15 sex- and age-matched pain-free control participants. A 2-limb forearm matching task in blindfolded participants, and a single-limb pointer task, with the reference limb hidden from view, was used to assess forearm position sense. Position sense was determined after muscle contraction or stretch, intended to induce a high or low spindle activity in the painful and nonpainful limbs, respectively. Unilateral upper and lower limb chronic pain groups produced position errors comparable with healthy control participants for position matching and pointer tasks. The results indicate that the painful and nonpainful limb are involved in limb-matching. Lateralized pain, whether in the arm or leg, does not influence forearm position sense.
|
The journal of pain
| 2,016 | 7 | 1 | 3 |
30,836,779 |
Gold nanoparticles and hepatitis B virus.
|
Hepatitis B virus (HBV) infection is one of the major health issues in the world presently with high tendency of leading to hepatocarcinoma, cirrhosis, and liver cancer, especially if not properly managed. It has been estimated that there are about 2 billion people with a serological profile of HBV infection, and 360 million patients worldwide living with chronic HBV-associated liver disease, hence the need to find an efficient and precise diagnosis technique to drive a robust treatment for Hepatitis B virus cannot be over emphasized. The emergence of analytical device like biosensor which combines biological and physicochemical element to detect HBV in screened samples has been very helpful in providing a timely intervention to tame this virus. This review focuses on the current state of biosensor researches with respect to various in-depth application of gold nanoparticle for the detection of hepatitis B virus (HBV).
|
Artificial cells, nanomedicine, and biotechnology
| 2,019 | 12 | 1 | 16 |
35,521,095 |
The simultaneous detection of the squamous cell carcinoma antigen and cancer antigen 125 in the cervical cancer serum using nano-Ag polydopamine nanospheres in an SERS-based lateral flow immunoassay.
|
The accurate analysis of tumor related biomarkers is extremely critical in the diagnosis of the early stage cervical cancer. Herein, we designed a novel and inexpensive surface-enhanced Raman scattering-based lateral flow assay (SERS-based LFA) strip with a single test line, which was applied for the rapid and sensitive quantitative simultaneous analysis of SCCA and CA125 in serum samples from patients with cervical cancer. In the presence of target antigens, the monoclonal antibody-coupled and Raman reporter-labeled nano-Ag polydopamine nanospheres (PDA@Ag-NPs) aggregated on the test line modified by the polyclonal antibody to form a double-antibody sandwich structure. The finite difference time domain simulation demonstrated that large number of "hot spots" was generated among the nanogaps of aggregated PDA@AgNPs, which resulted in a huge enhancement of the signal of the Raman reporters. Accordingly, the limit of detection was determined to be 7.156 pg mL
|
RSC advances
| 2,020 | 8 | 1 | 24 |
29,229,397 |
Di-acetyl creatine ethyl ester, a new creatine derivative for the possible treatment of creatine transporter deficiency.
|
Creatine is pivotal in energy metabolism of the brain. In primary creatine deficiency syndromes, creatine is missing from the brain. Two of them (AGAT and GAMT deficiency) are due to impaired creatine synthesis, and can be treated by creatine supplementation. By contrast, creatine transporter deficiency cannot be treated by such supplementation, since creatine crossing of biological membranes (plasma membrane and blood-brain barrier) is dependent on its transporter. This problem might be overcome by modifying the creatine molecule to allow it to cross biological membranes independently of its transporter. Thus, we designed and synthesized di-acetyl creatine ethyl ester (DAC), a compound that should cross biological membranes independently of the transporter due to its very high lipophilicity. We investigated its ability to increase intracellular creatine levels even after block of creatine transporter, and to counter cell damage induced by transporter block. In our experiments after block of the creatine transporter, DAC was able both to prevent electrophysiological failure and to increase intracellular creatine. Interestingly, it did so in micromolar concentrations, at variance with all the other creatine derivatives that we know of.
|
Neuroscience letters
| 2,018 | 2 | 1 | 9 |
30,782,625 |
XCalibur aneurysm occlusion device for the treatment of direct carotid cavernous fistula: expansion of armamentarium.
|
We report the first case of a post-traumatic direct carotid cavernous fistula (CCF) treated with the XCalibur aneurysm occlusion device, which is a balloon mounted stent with flow diversion effect. Two devices were deployed across the fistula in an overlapping manner, resulting in complete occlusion of the fistula. Flow diversion with this device can provide a safe and alternative treatment option in direct CCF.
|
BMJ case reports
| 2,019 | 2 | 0 | 5 |
23,407,949 |
HTR2 receptors in a songbird premotor cortical-like area modulate spectral characteristics of zebra finch song.
|
Serotonin [5-hydroxytryptamine (5-HT)] is involved in modulating an array of complex behaviors including learning, depression, and circadian rhythms. Additionally, HTR2 receptors on layer V pyramidal neurons are thought to mediate the actions of psychedelic drugs; the native function of these receptors at this site, however, remains unknown. Previously, we found that activation of HTR2 receptors in the zebra finch forebrain song premotor structure the robust nucleus of the arcopallium (RA) led to increased excitation, and that endogenous 5-HT could roughly double spontaneous firing rate. Here, using in vivo single-unit recordings, we found that direct application of 5-HT to these same RA projection neurons, which are analogous to layer V cortical pyramidal neurons, caused a significant increase in the number of action potentials per song-related burst, and a dramatic decrease in signal-to-noise ratio. Injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the third ventricle greatly reduced telencephalic 5-HT and resulted in decreased fundamental frequency of harmonic syllables as well as increased goodness of pitch. Both of these results can be explained by the observed actions of 5-HT on RA projection neurons, and both effects recovered to baseline within 2 weeks following the toxin injection. These results show that 5-HT is involved in modulating spectral properties of song, likely via effects on RA projection neurons, but that adult zebra finches can partially compensate for this deficit within 7 d.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,013 | 2 | 1 | 4 |
32,439,021 |
Neurodevelopmental Factors in Schizophrenia.
|
The onset of schizophrenia is usually in late adolescence or early adulthood. However, accumulating evidence has suggested that the disease condition is an outcome of gene-environment interactions that act in neural development during early life and adolescence. Some children who later develop schizophrenia have early developmental and educational and social challenges. Some patients with schizophrenia have an abundance of nonspecific neurologic soft signs and minor physical anomalies. Adolescence is a sensitive period of increased neuronal plasticity. It is important to consider early detection and intervention from the prodromal stage to early disease to prevent its devastating long-term consequences.
|
The Psychiatric clinics of North America
| 2,020 | 6 | 7 | 46 |
28,079,757 |
Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells.
|
Abdominal pain is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMCs), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (T13 to L2) were identified for patch-clamp and gene expression studies. Referred visceral sensitivity was assessed by measuring withdrawal response to stimulation by von Frey filaments in the lower abdomen. Membrane excitability of colon-projecting dorsal root ganglia neurons was significantly enhanced, and the withdrawal response to von Frey filament stimulation markedly increased in BO rats. The expression of NGF mRNA and protein was increased in a time-dependent manner (day 1-day 7) in colonic SMC but not in mucosa/submucosa of the obstructed colon. Mechanical stretch in vitro caused robust NGF mRNA and protein expression in colonic SMC. Treatment with anti-NGF antibody attenuated colon neuron hyperexcitability and referred hypersensitivity in BO rats. Obstruction led to significant increases of tetrodotoxin-resistant Na currents and mRNA expression of Nav1.8 but not Nav1.6 and Nav1.7 in colon neurons; these changes were abolished by anti-NGF treatment. In conclusion, mechanical stress-induced upregulation of NGF in colon SMC underlies the visceral hypersensitivity in BO through increased gene expression and activity of tetrodotoxin-resistant Na channels in sensory neurons.
|
Pain
| 2,017 | 4 | 4 | 22 |
30,894,142 |
Pyramidal system involvement in progressive supranuclear palsy - a clinicopathological correlation.
|
We aimed to produce a detailed neuropathological analysis of pyramidal motor system pathology and provide its clinical pathological correlation in cases with definite progressive supranuclear palsy (PSP).
|
BMC neurology
| 2,019 | 3 | 1 | 8 |
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