brain - derived neurotrophic factor ( bdnf ) is a neurotrophic factor that appears throughout 
 the mammalian central nervous system1 .
it is frequently found in the hippocampus of the brain ( hippocampal formation ) , as well as 
 in the cerebral cortex and amygdalus .
bdnf is reported to affect learning ability and 
 memory , as it operates in the areas that regulate neuronal growth , and repair and 
 neuroplasticity .
it is also a feature of the brain during brain formation before birth and 
 its influence continues through adolescence2,3,4 .
bdnf is reported to be an important material for the growth and development of nerve cells 
 in different areas both within and outside of the brain , increasing resistance to damage and 
 improving the survival of neurons1 .
it is 
 a key factor in growth and differentiation during neural development , and is often used as 
 an index to measure the impact of exercise on the rehabilitation of damaged nerves .
it is 
 further reported that both exercise and learning induce growth of the motor cortex , increase 
 in hippocampal bdnf , and increase in the plasticity of the brain , which in turn induces 
 development of the cell body and axon of the associated neurons5,6,7 .
bdnf expression in the hippocampus has been reported to improve the production and survival 
 of brain cells8 , and bdnf expression is 
 reported to be stimulated by exercise6 , 9 , 10 . 

it has also been reported that exercise has a positive impact on bdnf expression in the 
 animal brain11 . for young people , increases in bdnf induced by aerobic exercises would enhance neuronal 
 growth and development in the hippocampus , which would in turn enhance cognitive ability , 
 learning ability and memory , greatly improving educational performance .
therefore exercise 
 is considered to be essential for the development of the adolescent brain .
insulin - like growth factor 1 ( igf-1 ) , one of the factors involved in bdnf expression , is 
 known to mediate regulation of genes involved in bdnf - related neurogenesis12 , and it is involved in the growth and 
 differentiation of neuron units of the brain13 . in association with exercise ,
igf-1 increases in both the brain 
 and peripheral nerves after exercise and neurotransmitters are also increased in the blood 
 vessels14 . on the other hand , 

psychological stress has negative effects on nerve cells and heightened stress reduces bdnf 
 mrna expression6 . a fast - paced lifestyle , coupled with education policy and environmental changes in south 
 korea are thought to have increased the psychological stress of the korean youth population . 

corticotrophin - releasing factor ( crf ) is secreted by 
 the hypothalamus , which in turn induces the release of adrenocorticotrophic hormone ( acth ) 
 from the anterior pituitary .
cortisol is released not only in response to psychological stress , but also as a product of 
 the energy generation required for exercises . with exercise
, cortisol is released through 
 the hypothalamic - pituitary - adrenal axis into the circulation of the human body .
cortisol , 
 which is one of the major corticosteroids , plays a role in the conversion of glycogen in 
 muscles and the liver into blood glucose , or fats into fatty acids for the purpose of 
 metabolic energy production .
also , cortisol responds sensitively to self - defensive stimuli 
 such as psychological oppression , anxiety , or fear , similar to the response to energy 
 generation for the stimulation of movement .
the relationship between stress and bdnf mrna 
 ( messenger ribonucleic acid ) reveals that increased stress will lower the level of bdnf 
 expression6 and significantly disturbs 
 the creation of the nerve cells in the hippocampus15 .
most previous studies of bdnf have used experimental animals and many of their results 
 correlate with a particular disease . in those experiments ,
animals were forced to perform 
 aerobic exercises , with stress induced for the initiation and maintenance of the exercising 
 condition . when these animals are given a stimulating stressor , such as electrical shocks or 
 swimming as exercise ,
the stress elicits strong instincts to escape and initiates changes in 
 the peripheral circulation .
it also activates circulation in the central brain , thus 
 affecting the whole body .
in addition to the need to use a stressor to initiate exercise 
 conditions in animals , the results use of these animal models have obvious limitations 
 regarding their application to the human body . in order to investigate the effect of 
 cortisol on the expression of bdnf and igf-1 through aerobic exercise , such experiments must 
 ultimately be carried out using voluntary exercises performed by human subjects , negating 
 the need for stress induced exercise states which can confound results .
previous studies 
 have not yet sufficiently proved the relationship of cortisol expression and nerve cell 
 growth in response to aerobic exercise , as well as the involvement of bdnf and igf-1 .
the purpose of this study was therefore , to identify effect of aerobic exercise on the 
 expression of cortisol , bdnf and igf-1 related to nerve cell growth .
twenty healthy junior high school students , who did not regularly exercise and were not 
 previously diagnosed as having abnormal glucose metabolism volunteered to participate in the 
 study .
this study was approved and reviewed by the institutional review board of the human care 
 and use committee of the exercise physiology research institute of dankook university , and 
 written consent forms were obtained from all of the subjects parents .
bdnf , igf-1 , and cortisol levels of all the subjects were measured at the start of the 
 study .
after baseline measurement , the subjects were randomly assigned an exercise group ( n 
 = 10 ) or a control group ( n = 10 ) .
the characteristics of the subjects are shown in table 1table 1.the characteristics of the subjects ( msd)variables groupage ( yrs)height ( cm)body weight ( kg)%fateg ( n=10)15161.2  2.556.3  6.819.8  4.6cg ( n=10)15162.6  3.455.7  7.718.9  3.8eg : exercise group , cg : control group .
eg : exercise group , cg : control group the exercise group participated in 8 weeks of supervised aerobic exercise training .
the 
 exercise group trained for 3 days a week for 8 weeks , while the control group was asked to 
 continue their normal sedentary activities .
maximal oxygen uptake ( vo2max ) of all the 
 exercise group participants was measured in order to prescribe aerobic exercise intensity 
 for the purpose of the intervention .
the exercise group subjects were instructed to maintain a typical diet and a particular 
 activity pattern throughout the study , while the subjects in the control group were asked to 
 continue their daily normal and sedentary activities .
pre - assessment blood samples were obtained 2 days before , and 2 days after the end of the 
 exercise intervention for the assessment of bdnf , igf-1 , and cortisol ( table 2table 2.baseline values of bdnf , igf-1 , and cortisol in eg and cgvariableseg ( n=10)cg ( n=10)m  sdm  sdbdnf ( pg / ml)23,321.7  6,247.024,071.3  6,139.2igf-1 ( ng / ml)397.1  131.1420.0  172.3cortisol ( g / dl)13.6  4.114.5  4.6eg : exercise group , cg : control group .
there were no significant differences 
 ( independent t - test ) maximal oxygen uptake ( vo2max ) was measured using a computerized metabolic ( quinton , usa ) 
 and a modified bruce protocol at dankook university fitness center , korea .
graded exercise 
 assessment was stopped once subjects attained an rer  1.10 or if subjects indicated that 
 they wished to stop the test17 .
whole blood was centrifuged at 3,000  rpm for 15 minutes and to separate it into serum and 
 plasma .
bdnf concentration was measured using an elisa kit ( sandwich enzyme - linked immunosorbant 
 assay ) .
igf-1 and cortisol were measured using a -counter ( cobra-5010 quantum , packard , 
 usa ) .
elisa kits ( promega , usa ) , igf - i - ria - ct kits ( toshiba yba-200 frneo , japan ) and 
 coat - a - count cortisol kits ( siemens , usa ) were used to determine the concentrations of bdnf 
 ( pg / ml ) , igf-1 ( ng / ml ) and cortisol ( ng / ml ) , respectively .
the exercise program of this study consisted of an 8-week , 3 days a week aerobic exercise 
 regimen at dankook university fitness center in gyeonggi - do , korea .
pre - test vo2max , maximal 
 heart rate ( hrmax ) , and resting heart rates ( hrrest ) were measured by ecg supporting a 
 computerized metabolic ( quinton , usa ) .
exercise was performed on treadmills and the exercise intensity was set between 40% and 
 60%vo2r based on the scale recommended by acsm17 . in order to standardize the work performed , exercise time was 
 individually prescribed so that each subject burned 200  kcal in an exercise session . during the testing and intervention periods ,
all subjects were asked not to undertake any 
 exercise other than the ones designed for the experiments , with cooperation from their 
 schools .
all the results of this study are presented as mean  standard deviation . the independent 
 t - test
was performed to examine differences in baseline characteristics of the subjects 
 between the 2 groups .
the paired t - test was performed to examine the changes between pre- 
 and post - intervention in each group .
statistical significance was chosen as p < 0.05 , and 
 all analyses were performed using spss version 18.0 ( spss , chicago , il , usa ) .
the changes in bdnf , igf-1 and cortisol after exercising 3 days per week for 8 weeks are 
 shown in table 3table 3.the results of the paired t - test for bdnf , igf-1 , and a cortisolvariablesgrouppre - testpost - test(m  sd)(m  sd)bdnf ( pg / ml)eg23,321.7  6,247.027,566.0  5,647.6***cg24,071.3  6,139.224,921.2  7,821.5igf-1 ( ng / ml)eg397.1  131.1596.6  104.1*cg420.0  172.3432.3  165.2cortisol ( g / dl)eg13.6  4.111.2  2.3cg14.5  4.615.3  4.3values are meanssd .
* : significantly 
 different within group by the paired t - test , * : p < 0.05 , * * * : p < 0.001 .
* : significantly 
 different within group by the paired t - test , * : p < 0.05 , * * * : p < 0.001 after performing 8 weeks of aerobic exercise , the change in bdnf of the exercise group was 
 significant ( p < 0.01 ) , increasing from 23,321.7  6,247.0
the change in igf-1 was also significant ( p < 0.05 ) , increasing from 420.0  172.3 
 ng / ml to 432.3  165.2 ng / ml .
the change in cortisol , however , was not significant , 
 declining from 13.6  4.1  g / dl to 11.2  2.3  g / dl .
the control group did not show any 
 significant differences in bdnf , igr-1 or cortisol between pre- and post - intervention .
the differences in bdnf , igf-1 and cortisol after exercise are shown in table 4table 4.the significance of differences ( independent t - test ) between eg and cg after 8 
 weeks of exercisevariableseg ( n=10)cg ( n=10)msdmsdbdnf ( pg / ml)27,566.0  5,647.624,921.2  7,821.5**igf-1 ( ng / ml)596.6  104.1432.2  165.2*cortisol ( g / dl)11.2  2.315.3  4.3values are meanssd .
* : significantly 
 different by the independent t - test , * : p < 0.05 , * * : p < 0.01 .
* : significantly 
 different by the independent t - test , * : p < 0.05 , * * : p < 0.01
research has been actively conducted on changes in the secretion of bdnf as it relates to 
 brain function , so it is well known that bdnf is secreted in peripheral veins and skeletal 
 muscles as well as in various brain regions .
recently more research has been conducted to 
 measure the reaction of human serum bdnf levels and targeted cognitive function of adult and 
 elderly human subjects following long - term aerobic exercise and short sessions of aerobic 
 exercise18,19,20,21,22,23 .
uysal et al . reported that when the rats performed regular aerobic exercises the density of 
 hippocampal neurons in rats increased24 . 

, seven adult male subjects performed 12 weeks of endurance 
 aerobic exercise and as a result bdnf serum significantly increased25 .
examined the effects of both short and 
 long - term aerobic exercise on adolescents , whose brains are thought to still be undergoing 
 significant development21 .
they showed 
 enhanced bdnf expression as a result of a single session of aerobic exercise , and a higher 
 level of enhancement after the long - term aerobic exercise .
it has also been reported that 
 endurance exercise increases bdnf protein expression in the skeletal muscle of rodents26 .
reported increases in the 
 amount of bdnf as a result of long term regular exercise both when measured , during the 
 exercise and at rest compared to groups that did not exercise at all3 . in this study , after 8 weeks of regular aerobic exercise , the exercise group showed 
 significantly increased serum bdnf expression levels , and a significant difference compared 
 to the control group . in the study of erickson et al .
, 120 elderly subjects performed 40 
 minutes of walking exercise ( 5060% intensity ) for 7 weeks , and they demonstrated , 
 significant increases in maximal oxygen uptake , serum bdnf , cognitive ability , and the size 
 of the hippocampus20 .
also recent studies 
 have reported the tendency of bdnf to increase at rest when endurance aerobic exercise was 
 performed11 , 20 , 25 , 27 , 28 . however , a study by ferris et al . reported that cycling for a duration of 30 minutes at an 
 intensity of 55% vo2max ( 20% below the lactate threshold ) did not affect serum bdnf 
 concentrations29 .
we believe the , 
 increases in serum bdnf levels at rest and after regular aerobic exercise are related to the 
 intensity of the exercise , and a threshold intensity of 60% vo2max seems necessary to elicit 
 a response in bdnf levels .
more research should be done to further elucidate the 
 relationship between exercise intensity and bdnf expression in response to exercise .
studied the effects of both short- and long - term exercise21 , examining changes in serum bdnf levels 
 and cognitive performance .
they included the use of a face - name matching task test and a 
 colour - word test for cognitive performance evaluation ( memory ) .
only the group which 
 conducted 5 weeks of regular aerobic exercise showed a significant improvement in the 
 face - name matching task test .
previous studies have failed to identify a relationship 
 between the level of expression of bdnf and improvement in brain function in humans . 

therefore , future studies relating the expression of bdnf and measures of brain function 
 should also consider the effects of fifferent levels of exercise intensity on functional 
 improvements as well as bdnf .
igf-1 ( insulin - like growth factor 1 ) is reported to be a carrier located in the upper part 
 of a signaling pathway which induces the expression of bdnf .
igf-1 has been reported to be a 
 factor contributing to neural cell growth , differentiation and survival , and it shows 
 increases in expression in the brain and periphery in response to various forms of 
 exercise12 .
previous studies of the relationship between exercise and igf-1 have reported that growth 
 hormone increased due to regular aerobic exercise through the promotion of igf-1 synthesis 
 in cells .
it was reported that igf-1 increased through an interaction with a variety of 
 cells in the liver30 . in this study , 8 
 weeks of regular aerobic exercise resulted in a significant increase in serum igf-1 
 expression levels post - intervention , and the exercise group also showed significant 
 differences from the group that did not exercise regularly . in general , skeletal muscle growth and atrophy is regulated by insulin - like growth 
 factor-131 .
lee and rhyu reported that 
 igf-1 induced changes in the nervous system through aerobic exercise , which is a necessary 
 condition for increased bdnf expression .
they also showed that igf-1 was a carrier located 
 in the upper part of a signaling pathway which regulates the expression of bdnf32 .
also , larnon , avitzur and klinger 
 reported that physical activity acted in combination with growth hormones and intermediate 
 mediators to elicit changes in bdnf expression .
they further reported that when children or 
 young people are at rest , physical activity - associated changes in growth hormone induce 
 increases in the level of igf-1 through interactions with liver cells , which are important 
 for protein synthesis , bone growth , and cell proliferation33 .
cortisol is a stress hormone secreted from the adrenal cortex of the kidneys , and it is 
 expressed in response to external stimuli which induce psychological stress , and plays a 
 role in increasing blood pressure and glucose levels , enabling the body to produce maximum 
 energy as a part of the stress response mechanism .
a study of the relationship between exercise and cortisol showed that short - term medium to 
 low intensity strength exercises did not change plasma cortisol levels or may have even 
 slightly reduced these levels , whereas high - intensity exercises increased plasma cortisol 
 levels in the body34 . in the present study , the group which performed regular aerobic exercise for 8 weeks showed 
 decreased blood plasma cortisol levels , but the difference was not statistically 
 significant .
we believe this shows that while stress - induced exercise affects the expression 
 of cortisol , as described in the murine studies of zheng et al . , the negative relationship 
 between bdnf and cortisol is likely the result of changes in cortisol due to stress rather 
 than the exercise performed16 .
this study was conducted on adolescent subjects , whose brains were still undergoing 
 development , with the purpose of identifying the effect of an 8-week aerobic exercise 
 protocol on the expression of bdnf , igf-1 and cortisol . the results of this study suggest 
 that chronic aerobic exercise has a positive effect , enhancing resting serum bdnf and igf-1 
 expression in adolescents whose brains are still developing .
 [ purpose ] this study was conducted on adolescent subjects whose brains are still 
 developing with the purpose of identifying the effect of 8 weeks duration of aerobic 
 exercises on the expression of bdnf , igf-1 and cortisol , to identify effect of aerobic 
 exercise on the expression of cortisol , bdnf and igf-1 related to nerve cell growth . 
 [ 
 subjects and methods ] the subjects were 20 junior - high school students with no history of 
 physical illness . 
 the students were divided into an exercise group and a control group . 
 
 the exercise group performed 3 treadmill exercise times per week for 8 weeks . 
 the exercise 
 time for the consumption of 200  kcal was calculated and the exercises were performed by 
 each individual for 8 weeks . [ results ] the exercise group showed statistically significant 
 in increases serum bdnf and igf-1 after 8 weeks , but cortisol showed no significant 
 change . 
 there were statistically significant differences between the groups in serum bdnf 
 and igf-1 after 8 weeks , but the difference in cortisol levels was not significant . 
 
 [ conclusion ] we found that long - term regular aerobic exercises has a positive effect on 
 the enhancement of serum bdnf levels at rest and igf-1 of adolescents who are still 
 undergoing through brain developments . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION