Temporal variations in the gut microbial diversity in response to high-fat diet and exercise.

High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray-Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections.

Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/ß-Catenin Pathway in Autistic Mice.

PURPOSE: Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/ß-catenin signaling pathway. METHODS: On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, ß-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. RESULTS: Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of ß-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. CONCLUSION: Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/ß-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.

Treadmill exercise improves spatial learning ability by increasing cell proliferation in offspring born to maternal rats receiving stress during pregnancy.

Prenatal stress causes learning deficits by inhibiting neurogenesis in the hippocampus. We studied the effects of maternal treadmill running or offspring treadmill running on the spatial learning ability of adolescent offspring rats or adult offspring rats born to maternal rats that received stress during pregnancy. For this study, spatial learning ability was measured by radial 8-arm maze task. Immunohistochemistry for 5-bromo-2'-deoxyuridine and Western blot for brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were also conducted. Stress was induced by exposing pregnant rats to hound in an enclosed room. Maternal treadmill running or treadmill running of offspring improved spatial learning ability of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased hippocampal cell proliferation of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased BDNF and TrkB expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring inhibited Bax expression and increased Bcl-2 expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Mother's exercise during pregnancy or child's exercise after childbirth can improve the spatial learning ability deteriorated due to stress during pregnancy.

Effects of swimming exercise on social isolation-induced memory impairment and apoptosis in old rats.

Effect of swimming exercise on serotonin (5-hydroxytryptamine, 5-HT) expression and apoptosis in social isolation rats during old age was investigated. Rats in the old social isolation groups were housed alone per cage for 4 weeks. Rats in the swimming exercise groups were allowed to swim for 30 min once daily for 4 weeks. Morris water maze task determined spatial working memory and elevated plus maze test determined anxiety. Immunohistochemistry for tryptophan hydroxylase (TPH) and 5-HT in the dorsal raphe and for doublecortin (DCX) in the hippocampal dentate gyrus was conducted. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in the hippocampal dentate gyrus was performed. Western blot analysis for Bax, Bcl-2, and cytochrome c in the hippocampus was conducted. Social isolation in rats of old age reduced spatial working memory and increased anxiety level. Swimming exercise enhanced spatial working memory and suppressed anxiety level. Social isolation in rats of old age inhibited TPH and 5-HT expression in dorsal rape. Swimming exercise increased TPH and 5-HT expression. Social isolation in rats of old age inhibited DCX-positive cells in the hippocampal dente gyrus. Swimming exercise increased DCX-positive cells. Social isolation in rats of old age increased TUNEL-positive cells, Bax and cytochrome c expression, and decreased Bcl-2 expression, which promoted apoptosis. Swimming exercise suppressed TUNEL-positive cells, Bax and cytochrome c expression, and increased Bcl-2 expression, which inhibited apoptosis. Swimming exercise improved 5-HT expression and suppressed apoptosis to alleviate anxiety and memory impairment during old age.

Swimming exercise ameliorates mood disorder and memory impairment by enhancing neurogenesis, serotonin expression, and inhibiting apoptosis in social isolation rats during adolescence.

Social isolation during adolescence is associated with anxiety, depres-sion, and memory impairment. Exercise has been reported as a positive effect on brain function, especially hippocampus. The present study ex-amined the effect of swimming exercise on apoptosis, cell proliferation, and serotonin expression in social isolation rats during adolescence stage. Social isolation started at postnatal day 21 and continued for 6 weeks. The rats in the swimming group were forced to swim for 60 min once daily during 6 days per week for 6 consecutive weeks. The rats in the social isolation during adolescence showed anxiety, depression, short-term memory impairment. Social isolation facilitated apoptosis and inhibited cell proliferation and differentiation. Social isolation sup-pressed expression of serotonin, brain-derived neurotrophic factor, and tyrosine kinase B. Swimming exercise alleviated anxiety, depression, short-term impairment. Swimming exercise suppressed apoptosis, en-hanced neurogenesis, and increased serotonin expression. In our study, swimming exercise ameliorates mood disorder and memory impairment by enhancing neurogenesis and serotonin expression and inhibiting apoptosis in social isolation.

Cardiac adaptation to exercise training in health and disease.

The heart is the primary pump that circulates blood through the entire cardiovascular system, serving many important functions in the body. Exercise training provides favorable anatomical and physiological changes that reduce the risk of heart disease and failure. Compared with pathological cardiac hypertrophy, exercise-induced physiological cardiac hypertrophy leads to an improvement in heart function. Exercise-induced cardiac remodeling is associated with gene regulatory mechanisms and cellular signaling pathways underlying cellular, molecular, and metabolic adaptations. Exercise training also promotes mitochondrial biogenesis and oxidative capacity leading to a decrease in cardiovascular disease. In this review, we summarized the exercise-induced adaptation in cardiac structure and function to understand cellular and molecular signaling pathways and mechanisms in preclinical and clinical trials.

Wnt signaling pathway is implicated in the alleviating effect of treadmill exercise on maternal separation-induced depression.

Maternal separation in the developmental stage has a negative influence on brain development and causes depression. The extracellular ligand, Wnt, and its receptors play an important role in axis formation and neural development. Exercise inhibits apoptosis, increases cell proliferation, and exerts antidepressive effect. In this study, the effect of treadmill exercise on the maternal separation-induced depression was investigated in the aspect of Wnt signaling pathway. The maternal separation started on the postnatal day 14. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. The rat pups in the maternal separation and fluoxetine-treated group were intraperitoneally injected with 5-mg/kg fluoxetine once a day from postnatal day 21 to postnatal day 34. Forced swimming test was performed to evaluate the depression level. Western blotting was performed for the expressions of Wnt signaling ligands, Wnt2 and Wnt3a, and Wnt signaling inhibitors, Dkk1, and sFRP3. Maternal separation showed depressive behaviors in the forced swimming test. Treadmill exercise alleviated depressive behaviors in the maternal separation rat pups. Expressions of Wnt2 and Wnt3a were decreased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Wnt2 and Wnt3a expressions. Expressions of Dkk1 and sFRP3 in the hippocampus were increased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Dkk1 and sFRP3 expressions. Our study demonstrated that treadmill exercise activates Wnt signaling pathway, and then exerted antidepressive effect.

Effects of preconditioning exercise on nitric oxide and antioxidants in hippocampus of epileptic seizure.

The mechanism of epileptic seizure has not been identified clearly. Exercise can play a role of antioxidants against oxidative stress. In the present study, the neuroprotective effects of preconditioning exercise on epileptic seizure were investigated with focusing on antioxidants activity in the hippocampus. Rats were allocated to the following groups: saline control group, kainic acid control group, and previous exercise and kainic acid group. Rats in the previous exercise and kainic acid group were subjected to treadmill exercise 5 days a week for 4 weeks. After 48 hr of exercise period, rats in the kainic acid control group and previous exercise and kainic acid group were injected with kainic acid. The number of neuronal nitric oxide synthase-positive cells and the level of nitrite in hippocampus were increased and the expressions of superoxide dismutase-1, superoxide dismutase-2, and catalase in hippocampus were reduced in kainic acid control group compared with saline control group. By contrast, in the previous exercise and kainic acid group, the number of neuronal nitric oxide synthase-positive cells and the level of nitrite were decreased and the expressions of superoxide dismutase-1, superoxide dismutase-2, and catalase were increased compared with the kainic acid control group. Preconditioning exercise may have neuroprotective effects against oxidative stress via increased antioxidant activity in the hippocampus of epileptic seizure.

Treadmill exercise with bone marrow stromal cells transplantation facilitates neuroprotective effect through BDNF-ERK1/2 pathway in spinal cord injury rats.

Transplantation of bone marrow stromal cells (BMSCs) has been known as one of the effective therapeutic methods for functional recovery of spinal cord injury (SCI). Treadmill exercise also facilitates the functional recovery of SCI. Previously, we reported that combination of BMSCs transplantation with treadmill exercise potentiated the locomotor function in SCI rats. In the present study, we investigated whether recovery effect of BMSCs transplantation or treadmill exercise appears through the brain-derived neurotrophic factor (BDNF)-extracellular signal-regulated kinases 1/2 (ERK1/2) pathway. The spinal cord contusion injury was performed at the T9-T10 level using the impactor. Cultured BMSCs were transplanted directly into the lesion 1 week after SCI. Treadmill exercise was performed 6 days per a week for 6 weeks. Western blot for Bax, Bcl-2, BDNF, tyrosine kinase B (TrkB), and phosphorylated ERK1/2 (p-ERK1/2), phosphorylated JNK was performed. In the present results, combination of BMSCs transplantation with tread-mill exercise potently decreased Bax expression, potently increased Bcl-2 expression, and potently enhanced BDNF and TrkB expressions in the injured spinal cord. Combination of BMSCs transplantation with treadmill exercise further facilitated p-ERK1/2 and p-c-Jun expression levels. The present findings demonstrated the synergistic effect of treadmill exercise on neuroregenerative effect of BMSCs transplantation appeared through the activation of BDNF-ERK1/2 pathway in SCI.

Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats.

Brain inflammation is involved in many brain disorders, such as brain ischemic injury, Alzheimer diseases, and Parkinson disease. Physical exercise has been recommended for the prevention and treatment of many brain inflammatory diseases. In the present study, the effects of exercise on motor function in relation with apoptotic neuronal cell death following neuroinflammation were investigated. Moreover, we compared the effect of forced exercise with voluntary exercise on neuroinflammation-induced motor malfunction. For this study, rota-rod test, vertical pole test, foot fault test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for Bcl-2 and Bax were performed. Lipopolysaccharide was intraventricular infused for induction of brain inflammation. Treadmill exercise and wheel exercise were conducted during 6 weeks. In the present results, Treadmill exercise and wheel exercise alleviated brain inflammation-induced motor impairments by suppressing apoptotic neuronal cell death in the motor cortex. These effects of treadmill exercise and wheel exercise were similarly appeared.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study.

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

Effects of exercise on mature or precursor brain­derived neurotrophic factor pathways in ovariectomized rats.

Ovariectomy (OVX) is a method used to block estrogen in female rats that induces hippocampal dysfunction and affects brain­derived neurotrophic factor (BDNF) pathways. The majority of previous studies investigating OVX focused on BDNF expression in the hippocampus and cognitive function. The present study focused on the pathways of each BDNF type, precursor (proBDNF) and mature (mBDNF), and the effects of regular exercise in the hippocampus of ovariectomized rats. Female Sprague­Dawely rats were used and OVX surgery was performed. After 1 week of recovery from surgery, two groups of rats that received OVX surgery were subjected to regular treadmill exercise for 8 weeks. The results of protein levels by western blotting indicated that the expression of proBDNF, p75 neurotrophin receptor (p75NTR) and c­Jun N­terminal protein kinase (JNK) was increased, and mBDNF, tropomyosin­related kinase B (TrkB) and nuclear factor­κB expression was significantly reduced in the OVX control group compared with the sham control group SC (P<0.05). Thus, the survival pathway by mBDNF was impaired and the pro­apoptotic response was activated by increased JNK expression due to proBDNF­p75NTR binding in the hippocampus of ovariectomized rats. By contrast, exercise reduced activation of the pro­apoptotic response and increased mBDNF­TrkB expression in the hippocampus of ovariectomized rats. Thus, regular exercise may increase the activation of survival pathways via mBDNF and reducing the activation of the pro­apoptotic pathway of proBDNF in the hippocampus of ovariectomized rats.

Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups.

Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe using immunofluorescence. The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The present results demonstrated that social isolation increased resting time and decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and expression of BDNF and TrkB in the hippocampus were decreased by social isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was suppressed by social isolation. Treadmill exercise decreased resting time and increased mobility in the social isolated rat pups. Expression of 5-HT, TPH, BDNF, and TrkB was increased by treadmill exercise. The present results suggested that treadmill exercise may ameliorates social isolation-induced depression through increasing neuronal generation.

Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation.

PURPOSE: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. METHODS: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. RESULTS: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. CONCLUSIONS: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats.

Electromyography comparison of normal chair-desk system and assistant chair-desk system on fatigue.

[Purpose] This study was designed to test the effects of the Assistant Chair-Desk System (ACDS), which can reduce the forward tilt of the neck and trunk and the level of fatigue during long lasting study in the sitting position. [Subjects] Fourteen middle school students and 14 college students of mixed gender participated in this study. [Methods] Fatigue level, the trapezius muscle, and the forward tilt angle of the head and trunk as well as distance factors were assessed before after using a normal chair-desk system (NCDS) and the ACDS for 120 minutes. [Results] There was an interaction effect in the angle and length of the neck from the sitting posture changes after 2 hours of studying using the NCDS and ACDS. There were also significant differences in the fatigue levels, hip joint angles and the lengths from the head according to the main effects of the chair-systems. [Conclusion] The studying position while using the ACDS was determined to prevent significant fatigue levels of the muscle and body, provide support to the head, by limiting the forward movement of the neck, and prevent forward tilt of the neck and trunk, by enabling the target point and gaze to be closer to the horizontal direction.

Postnatal treadmill exercise attenuates prenatal stress-induced apoptosis through enhancing serotonin expression in aged-offspring rats.

Maternal stress during pregnancy affects negative impact on health of offspring. In the present study, we compared the effects of maternal treadmill exercise and offspring treadmill exercise on prenatal stress-induced apoptosis and serotonin expression in offspring. Stress to the pregnant rats was induced by exposure of maternal rats to the hunting dog in an enclosed room. Exposure time was 10 min, three times per day, with a 1-h interval between exposures. This regimen was maintained from the seventh day of gestation until delivery. The pregnant rats in the exercise group were forced to run on a motorized tread-mill for 30 min once a day, started 7 days after pregnancy until delivery. The offspring in the exercise group were forced to run on a motorized treadmill for 30 min once a day, started 4 weeks after birth for 4 weeks. In the present results, offspring exposed to prenatal stress exhibited lower Bcl-2 level and higher Bax level in the hippocampus, lower 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) expression in the dorsal raphe, and higher c-Fos expression in the locus coeruleus compared to age-matched control rats. Treadmill exercise of offspring suppressed Bax expression and enhanced Bcl-2 expression in the hippocampus, increased 5-HT and TPH expression in the dorsal raphe, and enhanced c-Fos expression in the locus coeruleus of offspring. Tread-mill exercise of offspring suppressed prenatal stress-induced apoptosis and normalized prenatal stress-induced alterations in serotonin synthesis and neuronal activation. However maternal treadmill exercise during pregnancy exerted no significant effect on offspring.

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice.

Schizophrenia is a chronic and severe mental disorder characterized by the disintegration of cognitive thought processes and emotional responses. Despite the precise cause of schizophrenia remains unclear, it is hypothesized that a dysregulation of the N­methyl­D­aspartate (NMDA) receptor in the brain is a major contributing factor to its development. Brain­derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is implicated in learning and memory processes. In the present study, we investigated in vivo the effects of voluntary wheel running on behavioral symptoms associated with NMDA receptor expression, using MK­801­induced schizophrenic mice. Abilify (aripiprazole), a drug used to treat human schizophrenia patients, was used as the positive control. For the assessment of behavioral symptoms affecting locomotion, social interaction and spatial working memory, the open­field, social interaction and Morris water maze tests were conducted. For investigating the biochemical parameters, NMDA receptor expression in the hippocampal CA2­3 regions and prefrontal cortex was detected by NMDA immunofluorescence and BDNF expression in the hippocampus was measured using western blot analysis. MK­801 injection for 14 days induced schizophrenia­like behavioral abnormalities with decreased expression of the NMDA receptor and BDNF in the brains of mice. The results indicated that free access to voluntary wheel running for 2 weeks alleviated schizophrenia­like behavioral abnormalities and increased the expression of NMDA receptor and BDNF, comparable to the effects of aripiprazole treatment. In the present study, the results suggest that NMDA receptor hypofunctioning induced schizophrenia­like behaviors, and that voluntary wheel running was effective in reducing these symptoms by increasing NMDA receptor and BDNF expression, resulting in an improvement of disease related behavioral deficits.

Treadmill exercise enhances NMDA receptor expression in schizophrenia mice.

Schizophrenia is a serious psychiatric disorder with several symptoms including cognitive dysfunction. Although the causes of schizophrenia are still unclear, there is a strong suspicion that the abnormality in N-methyl-D-aspartate (NMDA) receptor may contribute to schizophrenia symptoms. In the present study, the effect of treadmill exercise on the NMDA receptor expression was evaluated using MK-801-induced schizophrenia mice. Immunohistochemistry for expressions of NMDA receptor tyrosine hydroxylase (TH) was conducted. Western blot for brain-derived neurotrophic factor (BDNF) was also performed. In the present results, the mice in the MK-801-treated group displayed reduced NMDA receptor expression. Enhanced TH expression and suppressed BDNF expression were also observed in the MK-801-treated mice. Treadmill exercise improved NMDA receptor expression in the MK-801-induced schizophrenia mice. Treadmill exercise also suppressed TH expression and enhanced BDNF expression in the MK-801-induced schizophrenia mice. The present study showed that down-regulation of NMDA receptor demonstrated schizophrenia-like parameters, meanwhile treadmill running improved schizophrenia-related parameters through enhancing NMDA receptor expression.

Treadmill exercise exerts ameliorating effect on isolation-induced depression via neuronal activation.

Maternal isolation has been used as a valid animal model of early life stress, and it induces depression to offspring. Exercise ameliorates the incidence and severity of stress-related mood disorders, such as depression and anxiety. Here in this study, we investigated the effects of treadmill exercise on brain neuronal excitation in the rat pups with maternal isolation-induced depression. Forced swimming test and immunohistochemistry for glucocorticoid receptor and c-Fos in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were conducted. Maternal isolation lasted for 6 hours per day and was continued from postnatal day 1 to postnatal day 30. The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 10 consecutive days, starting from the postnatal day 21 until the postnatal day 30. In the present results, treadmill exercise alleviated depressive state in the maternal separated rat pups, as potently as fluoxetine treatment. Treadmill exercise also restored the expressions of glucocorticoid receptor and c-Fos in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus of the maternal separated rat pups near to the control level, as fluoxetine treatment. The present study suggests the possibility that treadmill exercise can be used as the therapeutic strategy for the childhood depression induced by disturbed mother-child relationship.

Treadmill exercise alleviates prenatal noise stress-induced impairment of spatial learning ability through enhancing hippocampal neurogenesis in rat pups.

Stress alters brain cell properties and then disturbs cognitive processes, such as learning and memory. In this study, we investigated the effect of postnatal treadmill exercise on hippocampal neurogenesis and spatial learning ability of rat pups following prenatal noise stress. The impact of exercise intensity (mild-intensity exercise vs heavy-intensity exercise) was also compared. The pregnant rats in the stress-applied group were exposed to a 95 dB supersonic machine sound for 1 h once a day from the 15th day after mating until delivery. After birth, the rat pups in the exercise groups were made to run on a treadmill for 30 min once a day for 7 consecutive days, starting 4 weeks after birth. The spatial learning ability was tested using radial-arm maze task and hippocampal neurogenesis was determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. The rat pups born from the stress-applied maternal rats spent more time for the seeking of water and showed higher number of error in the radial-arm maze task compared to the control group. These rat pups showed suppressed neurogenesis in the hippocampus. In contrast, the rat pups performed postnatal treadmill exercise saved time for seeking of water and showed lower number of error compared to the stress-applied group. Postnatal treadmill exercise also enhanced neurogenesis in the hippocampus. The mild-intensity exercise showed more potent impact compared to the heavy-intensity exercise. The present results reveal that postnatal treadmill exercise lessens prenatal stress-induced deterioration of brain function in offspring.