menopausal period in women is characterized with a considerable decrease of estrogen hormonal level ( 1 - 3 ) .
the decrease of estrogen hormone ( hypoestrogenicity ) interrupts the normal functioning of female organs , including the brain ( 2 , 3 )
. low level of estrogen in the brain results in the decrease of cognitive , affective , nociceptive , movement , and motor coordination functions ( 4 ) .
these alterations of movement and motor coordination functions , which are pivotal functions of cerebellum ( 5 ) , indicate that cerebellum appears to be a target organ of estrogen .
it seems that the function of cerebellum is strongly influenced by hormonal status ( 6 ) . in rodents ,
menopausal - induced reduction of estrogen level can be appropriately mimicked by bilateral ovariectomy procedure .
adult mice underwent ovariectomy have been shown to suffer from sensorimotor ( including equilibrium capacity ) and exploratory behavior deficits comparable to their old counterparts .
these behavioral impairments were apparently associated with the decrease of plasma estradiol levels ( 7 ) .
previous studies have also shown a decrease in total protein synthesis ( 8) , an increase in estrogen receptor -mrna containing purkinje cells ( 9 ) , but no change in estrogen receptor  ( er ) ( 10 ) in the cerebellum of ovariectomized rats .
the physiological effects of estrogens in the brain are accomplished through genomic pathway ( 1 , 11 ) which are mediated by two estrogen receptors , i.e. er and estrogen receptor  ( er ) ( 12 ) . both er and er
however , the physiological effects of estrogen in cerebellum of adults are mainly mediated by er ( 13 ) .
several investigations discovered that physical exercise accelerates motor coordination improvement in both humans and animals ( 15 - 17 ) .
physical exercise was also observed to be associated with increased extragonadal aromatization ( 18 ) and neurotrophin synthesis ( 19 - 21 ) , all of which affect estrogen receptors expression ( 18 , 22 - 24 ) .
it remains unclear , however , whether physical exercise affects motor coordination performance , cerebellar and serum estradiol levels , as well as er in ovariectomized adult rats ; and how these variables correlate to each other .
ten female sprague dawley rats aged 12 weeks old which were initially weighing 170 - 200 g , were used in this study .
sprague dawley strain was chosen as experimental animals since this strain is considered to be suitable for studies on hormonal changes ( 25 ) .
the experimental protocol and animal handling was approved by the ethics committee of faculty of medicine , gadjah mada university ( approval number ke / fk/194/ec ) .
the rats were randomly assigned into two groups , i.e. exercise group ( n=5 ) , and control group ( n=5 ) .
after one week of acclimatization , both ovaries of all rats of both groups were removed via a 23 cm ventral midline incision on the abdomen under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) .
the exercise protocol referred to that adopted by hao et al ( 18 ) with slight modifications .
briefly , the protocol consisted of two periods , i.e. adaptation period and exercise period .
the rats of exercise group were adapted to the exercise protocol and treadmill apparatus ( gama tread version 2010 , faculty of medicine , gadjah mada university ) in a training room for one week . during the adaptation period , the running speed , the treadmill slope , and the duration of exercise were increased gradually .
the speed was increased from 10 m / min up to 18 m / min ; the slope was increased from 0 up to 5 ; while the duration was increased from 15 min up to 60 min .
subsequently , during the exercise period the rats were trained to keep running constantly on the treadmill at a speed of 18 m / min and at a slope of 5 for a total duration of 60 min per day .
this regimen of exercise was designed to be of moderate intensity and was calculated to obtain vo2 max of approximately 56% , based on the regimen developed by bupha - intr et al ( 26 ) .
the exercise was performed five times per week ( every mondays , tuesdays , wednesdays , fridays , and saturdays ) for 12 weeks with two days of rest period in each week ( every thursdays and sundays ) .
the control group was only moved to the training room at the same time when the exercise group performed exercise .
the motor coordination of rats was assessed on a rotarod apparatus ( the ugo basile model 7700 , veresi , italy ) .
the protocol of rotarod test was based on those described in previous studies ( 15 , 27 , 28 ) with slight modifications .
the tests were carried out in two series , namely seven days after ovariectomy and on the last day of exercise .
each series consisted of three trials , which were performed at the intervals of 60 min ( 15 ) .
the duration of each trial was 3 min ( 27 , 28 ) . in order to habituate to the apparatus , prior to the tests ,
each rat was left for 1 min on the running surface of the stationary rotarod .
the rat was then removed from the rotarod and the rotarod was turned on to rotate at a speed of 16 rounds per min .
it had to walk forward in order to maintain its position on the running surface of the rotarod during the three minutes trial .
the number of falls was defined as the average of the total number of falls of the rats during the three trials of each series .
prior to euthanasia , 2 ml of blood was collected from retro - orbital sinus of each rat under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) and it was allowed to clot for 2 hr at room temperature .
the blood was subsequently centrifuged at 1800 g for 10 min at a temperature of 4 c ( 29 ) .
serum was separated from the blood and stored at -20 c freezer prior to estrogen level measurements . immediately after blood collection
, the cerebellums of the rats were removed from their skulls and subdivided into left and right parts .
the extracted left cerebellums were homogenized in tegm ( 10 mm tris - hcl , 5 mm edta , 10% glycerol , and 2.3 mm mgcl ; ph 6.8 ) .
the homogenates were then centrifuged at 1000 g for 20 min , and the supernatants were used for the determination of er concentration .
the concentration was determined using rat estrogen receptor 2 ( er beta ) elisa kit ( cusabio biotech co. , ltd .
, pr china ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the concentration was determined using rat estradiol elisa kit ( drg instruments gmbh , germany ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the data of body weights of rats were analyzed using mann - whitney test , since these data did not pass the normality test .
on the other hand , the data of cerebellar weights were analyzed using unpaired t - test , since these data passed the normality and variance tests .
the mean differences of the number of falls before and after treatment ( within groups ) for both exercise and control groups were analyzed using paired t - test .
the differences of the number of falls between groups were analyzed using unpaired t - test .
in addition , unpaired t - test was used to measure the mean differences of serum and cerebellar estrogen as well as cerebellar er levels between groups .
spearman correlation test was used to assess the correlation between the number of falls and the levels of cerebellar and serum estrogen as well as er levels .
all data were presented in meansstandard error of mean ( sem ) and significance levels were set at p<0.05 .
ten female sprague dawley rats aged 12 weeks old which were initially weighing 170 - 200 g , were used in this study .
sprague dawley strain was chosen as experimental animals since this strain is considered to be suitable for studies on hormonal changes ( 25 ) .
the experimental protocol and animal handling was approved by the ethics committee of faculty of medicine , gadjah mada university ( approval number ke / fk/194/ec ) .
the rats were randomly assigned into two groups , i.e. exercise group ( n=5 ) , and control group ( n=5 ) .
after one week of acclimatization , both ovaries of all rats of both groups were removed via a 23 cm ventral midline incision on the abdomen under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) .
the exercise protocol referred to that adopted by hao et al ( 18 ) with slight modifications .
briefly , the protocol consisted of two periods , i.e. adaptation period and exercise period .
the rats of exercise group were adapted to the exercise protocol and treadmill apparatus ( gama tread version 2010 , faculty of medicine , gadjah mada university ) in a training room for one week . during the adaptation period , the running speed , the treadmill slope , and the duration of exercise were increased gradually .
the speed was increased from 10 m / min up to 18 m / min ; the slope was increased from 0 up to 5 ; while the duration was increased from 15 min up to 60 min .
subsequently , during the exercise period the rats were trained to keep running constantly on the treadmill at a speed of 18 m / min and at a slope of 5 for a total duration of 60 min per day .
this regimen of exercise was designed to be of moderate intensity and was calculated to obtain vo2 max of approximately 56% , based on the regimen developed by bupha - intr et al ( 26 ) .
the exercise was performed five times per week ( every mondays , tuesdays , wednesdays , fridays , and saturdays ) for 12 weeks with two days of rest period in each week ( every thursdays and sundays ) .
the control group was only moved to the training room at the same time when the exercise group performed exercise .
the motor coordination of rats was assessed on a rotarod apparatus ( the ugo basile model 7700 , veresi , italy ) .
the protocol of rotarod test was based on those described in previous studies ( 15 , 27 , 28 ) with slight modifications .
the tests were carried out in two series , namely seven days after ovariectomy and on the last day of exercise .
each series consisted of three trials , which were performed at the intervals of 60 min ( 15 ) .
the duration of each trial was 3 min ( 27 , 28 ) . in order to habituate to the apparatus , prior to the tests ,
each rat was left for 1 min on the running surface of the stationary rotarod .
the rat was then removed from the rotarod and the rotarod was turned on to rotate at a speed of 16 rounds per min .
it had to walk forward in order to maintain its position on the running surface of the rotarod during the three minutes trial .
the number of falls was defined as the average of the total number of falls of the rats during the three trials of each series .
prior to euthanasia , 2 ml of blood was collected from retro - orbital sinus of each rat under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) and it was allowed to clot for 2 hr at room temperature .
the blood was subsequently centrifuged at 1800 g for 10 min at a temperature of 4 c ( 29 ) .
serum was separated from the blood and stored at -20 c freezer prior to estrogen level measurements . immediately after blood collection
, the cerebellums of the rats were removed from their skulls and subdivided into left and right parts .
the extracted left cerebellums were homogenized in tegm ( 10 mm tris - hcl , 5 mm edta , 10% glycerol , and 2.3 mm mgcl ; ph 6.8 ) .
the homogenates were then centrifuged at 1000 g for 20 min , and the supernatants were used for the determination of er concentration .
the concentration was determined using rat estrogen receptor 2 ( er beta ) elisa kit ( cusabio biotech co. , ltd .
, pr china ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the concentration was determined using rat estradiol elisa kit ( drg instruments gmbh , germany ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the data of body weights of rats were analyzed using mann - whitney test , since these data did not pass the normality test .
on the other hand , the data of cerebellar weights were analyzed using unpaired t - test , since these data passed the normality and variance tests .
the mean differences of the number of falls before and after treatment ( within groups ) for both exercise and control groups were analyzed using paired t - test .
the differences of the number of falls between groups were analyzed using unpaired t - test .
in addition , unpaired t - test was used to measure the mean differences of serum and cerebellar estrogen as well as cerebellar er levels between groups .
spearman correlation test was used to assess the correlation between the number of falls and the levels of cerebellar and serum estrogen as well as er levels .
all data were presented in meansstandard error of mean ( sem ) and significance levels were set at p<0.05 .
ten female sprague dawley rats aged 12 weeks old which were initially weighing 170 - 200 g , were used in this study .
sprague dawley strain was chosen as experimental animals since this strain is considered to be suitable for studies on hormonal changes ( 25 ) .
the experimental protocol and animal handling was approved by the ethics committee of faculty of medicine , gadjah mada university ( approval number ke / fk/194/ec ) .
the rats were randomly assigned into two groups , i.e. exercise group ( n=5 ) , and control group ( n=5 ) .
after one week of acclimatization , both ovaries of all rats of both groups were removed via a 23 cm ventral midline incision on the abdomen under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) .
the exercise protocol referred to that adopted by hao et al ( 18 ) with slight modifications .
briefly , the protocol consisted of two periods , i.e. adaptation period and exercise period .
the rats of exercise group were adapted to the exercise protocol and treadmill apparatus ( gama tread version 2010 , faculty of medicine , gadjah mada university ) in a training room for one week . during the adaptation period
, the running speed , the treadmill slope , and the duration of exercise were increased gradually .
the speed was increased from 10 m / min up to 18 m / min ; the slope was increased from 0 up to 5 ; while the duration was increased from 15 min up to 60 min .
subsequently , during the exercise period the rats were trained to keep running constantly on the treadmill at a speed of 18 m / min and at a slope of 5 for a total duration of 60 min per day .
this regimen of exercise was designed to be of moderate intensity and was calculated to obtain vo2 max of approximately 56% , based on the regimen developed by bupha - intr et al ( 26 ) .
the exercise was performed five times per week ( every mondays , tuesdays , wednesdays , fridays , and saturdays ) for 12 weeks with two days of rest period in each week ( every thursdays and sundays ) .
the control group was only moved to the training room at the same time when the exercise group performed exercise .
the motor coordination of rats was assessed on a rotarod apparatus ( the ugo basile model 7700 , veresi , italy ) .
the protocol of rotarod test was based on those described in previous studies ( 15 , 27 , 28 ) with slight modifications .
the tests were carried out in two series , namely seven days after ovariectomy and on the last day of exercise .
each series consisted of three trials , which were performed at the intervals of 60 min ( 15 ) .
the duration of each trial was 3 min ( 27 , 28 ) . in order to habituate to the apparatus , prior to the tests ,
each rat was left for 1 min on the running surface of the stationary rotarod .
the rat was then removed from the rotarod and the rotarod was turned on to rotate at a speed of 16 rounds per min .
it had to walk forward in order to maintain its position on the running surface of the rotarod during the three minutes trial .
the number of falls was defined as the average of the total number of falls of the rats during the three trials of each series .
the rats were euthanized approximately 24 hr after the last exercise training . prior to euthanasia , 2 ml of blood
was collected from retro - orbital sinus of each rat under anesthesia ( ketamine hcl 40 mg / kg body weight ; pt guardian pharmatama , jakarta , indonesia ) and it was allowed to clot for 2 hr at room temperature . the blood was subsequently centrifuged at 1800 g for 10 min at a temperature of 4 c ( 29 ) .
serum was separated from the blood and stored at -20 c freezer prior to estrogen level measurements . immediately after blood collection
, the cerebellums of the rats were removed from their skulls and subdivided into left and right parts .
the extracted left cerebellums were homogenized in tegm ( 10 mm tris - hcl , 5 mm edta , 10% glycerol , and 2.3 mm mgcl ; ph 6.8 ) .
the homogenates were then centrifuged at 1000 g for 20 min , and the supernatants were used for the determination of er concentration .
the concentration was determined using rat estrogen receptor 2 ( er beta ) elisa kit ( cusabio biotech co. , ltd . , pr china ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the concentration was determined using rat estradiol elisa kit ( drg instruments gmbh , germany ) in a biorad microplate reader ( benchmark , japan ) operated at a wavelength of 450 nm .
the data of body weights of rats were analyzed using mann - whitney test , since these data did not pass the normality test .
on the other hand , the data of cerebellar weights were analyzed using unpaired t - test , since these data passed the normality and variance tests .
the mean differences of the number of falls before and after treatment ( within groups ) for both exercise and control groups were analyzed using paired t - test .
the differences of the number of falls between groups were analyzed using unpaired t - test .
in addition , unpaired t - test was used to measure the mean differences of serum and cerebellar estrogen as well as cerebellar er levels between groups .
spearman correlation test was used to assess the correlation between the number of falls and the levels of cerebellar and serum estrogen as well as er levels .
all data were presented in meansstandard error of mean ( sem ) and significance levels were set at p<0.05 .
table 1 presents data on the body and cerebellar weights of all rats . there was no significant difference of body weights between groups both before and after exercise .
the body and cerebellar weights in control and trained ovariectomized rats values are expressed as medians values are expressed as meanssem mann - whitney test ( between groups ) unpaired t - test test ( between groups ) table 2 presents data on the number of falls in motor coordination task before and after exercise in both control and exercise groups . there was no significant difference in the number of falls between groups before exercise . on the other hand ,
the number of falls of exercise groups was significantly lower than that of control group ( p<0.05 ) following exercise . in the exercise group ,
in contrast , in the control group , the number of falls after treatment was significantly higher than that before treatment .
effect of exercise training on the number of falls in motor coordination test before and after treatment in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups ) p - values of paired t - test ( within groups ) table 3 shows data on the serum and cerebellar estrogen as well as cerebellar er levels in both control and exercise groups .
the levels of cerebellar estrogen were significantly higher in the exercise group than in the control group .
on the other hand , there were no significant differences in the serum estrogen and cerebellar er levels between exercise and control groups .
effect of exercise training on the levels of serum and cerebellar estrogen and cerebellar er in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups ) spearman correlation test showed that there was a significantly negative correlation between the number of falls and cerebellar estrogen levels ( r= ( - ) 0.650 ; p= 0.042 ) .
however , no correlation between the number of falls and cerebellar er levels ( r= ( + ) 0.49 ; p= 0.893 ) as well as between the number of falls and serum estrogen level ( r= ( + ) 0.36 ; p= 0.920 ) was found .
table 1 presents data on the body and cerebellar weights of all rats . there was no significant difference of body weights between groups both before and after exercise .
the body and cerebellar weights in control and trained ovariectomized rats values are expressed as medians values are expressed as meanssem mann - whitney test ( between groups ) unpaired t - test test ( between groups ) table 2 presents data on the number of falls in motor coordination task before and after exercise in both control and exercise groups . there was no significant difference in the number of falls between groups before exercise . on the other hand ,
the number of falls of exercise groups was significantly lower than that of control group ( p<0.05 ) following exercise . in the exercise group ,
in contrast , in the control group , the number of falls after treatment was significantly higher than that before treatment .
effect of exercise training on the number of falls in motor coordination test before and after treatment in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups ) p - values of paired t - test ( within groups ) table 3 shows data on the serum and cerebellar estrogen as well as cerebellar er levels in both control and exercise groups .
the levels of cerebellar estrogen were significantly higher in the exercise group than in the control group .
on the other hand , there were no significant differences in the serum estrogen and cerebellar er levels between exercise and control groups .
effect of exercise training on the levels of serum and cerebellar estrogen and cerebellar er in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups ) spearman correlation test showed that there was a significantly negative correlation between the number of falls and cerebellar estrogen levels ( r= ( - ) 0.650 ; p= 0.042 ) .
however , no correlation between the number of falls and cerebellar er levels ( r= ( + ) 0.49 ; p= 0.893 ) as well as between the number of falls and serum estrogen level ( r= ( + ) 0.36 ; p= 0.920 ) was found .
table 1 presents data on the body and cerebellar weights of all rats . there was no significant difference of body weights between groups both before and after exercise .
the body and cerebellar weights in control and trained ovariectomized rats values are expressed as medians values are expressed as meanssem mann - whitney test ( between groups ) unpaired t - test test ( between groups )
table 2 presents data on the number of falls in motor coordination task before and after exercise in both control and exercise groups .
on the other hand , the number of falls of exercise groups was significantly lower than that of control group ( p<0.05 ) following exercise . in the exercise group ,
in contrast , in the control group , the number of falls after treatment was significantly higher than that before treatment .
effect of exercise training on the number of falls in motor coordination test before and after treatment in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups ) p - values of paired t - test ( within groups )
table 3 shows data on the serum and cerebellar estrogen as well as cerebellar er levels in both control and exercise groups .
the levels of cerebellar estrogen were significantly higher in the exercise group than in the control group .
on the other hand , there were no significant differences in the serum estrogen and cerebellar er levels between exercise and control groups .
effect of exercise training on the levels of serum and cerebellar estrogen and cerebellar er in the exercise and control ovariectomized rats p - values of unpaired t - test ( between groups )
spearman correlation test showed that there was a significantly negative correlation between the number of falls and cerebellar estrogen levels ( r= ( - ) 0.650 ; p= 0.042 ) .
however , no correlation between the number of falls and cerebellar er levels ( r= ( + ) 0.49 ; p= 0.893 ) as well as between the number of falls and serum estrogen level ( r= ( + ) 0.36 ; p= 0.920 ) was found .
the present study found that a regularly and lengthy period of physical exercise prevented ovariectomy - induced motor coordination performance deficits in rats .
in addition , motor coordination performance correlated significantly with cerebellar estrogen levels . we can not compare our study with others since literature search in the biomedical research database to date does not reveal any study of the effects of ovariectomy on the behavior of rats similar to ours .
the only study on rodents which may be comparable to ours is that of baeza and colleagues ( 7 ) .
our study corroborates this study in which ovariectomy brought about the decrease of sensorimotor abilities such as reflex , balance , muscle strength , and motor coordination in adult mice .
such deficits of motor coordination performance might be reversed by physical exercise as was shown in previous studies using rats model of cerebellar injury and ataxia ( 15 , 30 ) .
physical exercise , a type of physical activity assumed in a planned and structured movement to maintain or improve physical fitness ( 31 ) , may modify motor coordination function by affecting neuronal plasticity of cerebellum ( 32 ) , a key part of brain participating in regulating motor coordination ( 5 ) .
it is plausible that the effects of physical exercise on cerebellum are mediated through estrogen , as the present study demonstrated that cerebellar estrogen levels , but not serum estrogen levels , had a significantly negative correlation with motor coordination performance .
estrogen may influence cerebellum ( 4 ) by preventing neuronal deaths , inducing the formation of synapses and increasing information transmission through nerve impulses ( 33 , 34 ) as well as maintaining the structure ( 1 , 35 ) and function of cerebellum ( 34 ) . at the time of shortage of estrogen in the body , such as following ovariectomy or menopausal period , serum estrogen level may decline .
however , estrogen level in tissues , including in the cerebellum , might be maintained through extragonadal production in order to ensure the sufficient availability of estrogen for normal functioning of steroid - dependent organs .
it has been demonstrated that cerebellum is an organ that can produce steroid hormones de novo ( 36 ) .
estrogen biosynthesis in the cerebellum might be enabled by the presence of p450 aromatase enzyme ( 29 ) .
it has been put forth that p450 aromatase enzyme is responsible for converting testosterone into estradiol , and androstenedione into estron ( 37 - 39 ) .
previous studies in our laboratory have indicated that regular exercise might give rise to an increase of cyp19 aromatase expressions in adrenal cortex and adipose tissues of ovariectomized rats ( unpublished results ) .
cyp19 aromatase is thought to be implicated in the production of p450 aromatase enzyme ( 40 ) .
the precise mechanism of how exercise increases cerebellar estrogen levels by extragonadal aromatization remains unclear , but it may involve il-6 . physical exercise increases
skeletal muscle s production of ll-6 that are subsequently released in large quantities into the circulation ( 41 ) .
it has also been reported that ll-6 was released in human brain following a 60 min - physical exercise ( 42 ) .
il-6 in circulation triggers extragonadal steroidogenesis by increasing aromatase activity in the adrenal cortex , bone , and fat tissue ( 43 ) .
in addition , it is considered to be involved in the regulation of neurosteroid synthesis in the brain ( 44 ) .
estrogen normally mediates its functions via estrogen receptors ( er ) ( 12 , 34 , 37 ) .
direct genomic pathway which involves the interaction between er and its ligand ( estrogen ) is the common mechanism of estrogen action on brain tissue ( 1 , 35 ) . in adolescent cerebellum ,
furthermore , ers are more widely distributed in various types of cells of the cerebellar cortex ( 14 , 46 ) , whilst ers seem to be more confined to purkinje cells only ( 13 ) .
hence , it had been anticipated that , consistent with the increase of cerebellar estrogen levels , the cerebellar er levels also increased accordingly . however ,
the fact that er levels remained constant following regular exercise raises questions of whether estrogen might actually have exerted its effects through ers instead of ers .
previous studies have shown that the expression of er in neurons at the central nervous system is regulated by insulin - like growth factor - i ( igf - i ) ( 47 ) and depends on estrogen concentration ( 47 , 48 ) . in a circumstance
when estrogen in tissue is lacking , igf-1 increases the transcriptional activity of er. otherwise , if the tissue estrogen level is sufficient , igf-1 suppresses the transcriptional activity of er through phosphatidylinositol 3-kinase ( pi3k ) pathway
. meanwhile , er is a target gene of the transcriptional activity of er ( 49 ) .
this implies that the expression of er may actually reflect to that of er. in the present study , the higher estrogen level in the exercise group as compared to control group may suppress the transcriptional activity of both ers .
the present study found that regular physical exercise prevents ovariectomized - induced deterio - ration of motor coordination and cerebellar estrogen levels of rats .
nevertheless the precise mechanisms by which exercise and estrogen alter cerebellar functioning require further investi - gations .
 objective(s):the present study aims at examining the motor coordination performance , serum and cerebellar estrogen , as well as er levels , of ovariectomized rats ( as menopausal model ) following regular exercise.materials and methods : ten female sprague dawley rats aged 12 weeks old were randomly divided into two groups ; all of which underwent ovariectomy . 
 the first group was treated with regular exercise of moderate intensity , in which the rats were trained to run on a treadmill for 60 min per day for 12 weeks . 
 the second group served as control . 
 rotarod test was carried out before and after exercise treatment . 
 all rats were euthanized thereafter , and blood and cerebellums of the rats were collected . 
 the serum and cerebellar estrogen as well as cerebellar er levels were measured using elisa assays.results:the number of falls in the rotarod task of the exercise group was significantly lower than that of control group . 
 the cerebellar estrogen level of the exercise group was significantly higher than that of control group . 
 accordingly , there was a significantly negative correlation between the number of falls and cerebellar estrogen level in the exercise group.conclusion:the present study shows that a lengthy period of regular exercise improves the cerebellar estrogen level and motor coordination performance in ovariectomized rats . 
Introduction
Materials and Methods
None
Animals
Exercise training protocol
Rotarod task
Serum and tissue collection
Statistical analysis
Results
None
Body and cerebellar weights
Rotarod test
Levels of estrogen and cerebellar ER
Correlation
Discussion
Conclusion