Tae-Beom Seo

Effect of treadmill exercise on Purkinje cell loss and astrocytic reaction in the cerebellum after traumatic brain injury

The cerebellum is one of the brain areas, which is selectively vulnerable to forebrain traumatic brain injuries (TBI). Physical exercise in animals is known to promote cell survival and functional recovery after brain injuries. However, the detailed pathologic and functional alterations by exercise following an indirect cerebellar injury induced by a TBI are largely unknown. We determined the effects of treadmill exercise on survival of Purkinje neurons and on a population of reactive astrocytes in the gyrus of lobules VIII and IX of the cerebellum after TBI. The rats were divided into four groups: the sham-operation group, the sham-operation with exercise group, the TBI-induction group, and the TBI-induction with exercise group. Cell biological changes of Purkinje neurons following indirect cerebellar injury were analyzed by immunohistochemistry. TBI-induced loss of calbindin-stained Purkinje neurons in the posterior region of the cerebellum and TBI also increased formation of reactive astroyctes in both the granular and molecular layers of the cerebellar posterior region. Treadmill exercise for 10 days after TBI increased the number of calbindin-stained Purkinje neurons and suppressed formation of reactive astroyctes. The present study provides the possibility that treadmill exercise may be an important mediator to enhance survival of Purkinje neurons in TBI-induced indirect cerebellar injury.

Treadmill exercise improves behavioral outcomes and spatial learning memory through up-regulation of reelin signaling pathway in autistic rats

Autism is a complex neurodevelopmental disability with impairments of social interaction and communication, and repetitive behavior. Reelin is an extracellular glycoprotein that is essential for neuronal migration and brain development. Neuroprotective effects of exercise on various brain insults are well documented, however, the effects of exercise on autism in relation with reelin expression are not clarified. In the present study, we investigated the effects of treadmill exercise on the functional recovery and on the expressions of reelin and its downstream molecules, phosphatidylinositol-3-kinase (PI3K), phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated protein kinase 1 and 2 (p-ERK1/2), using autistic rats. For the induction of autism-like animal model, 400 mg/kg valproic acid was subcutaneously injected into the rats on the postnatal day 14. The rat in the treadmill exercise groups were forced to run on a treadmill for 30 min once a day, five times a week for 4 weeks, starting postnatal day 28. To investigate autism-like behaviors and memory deficit, open field, social interaction, and radial 8-arm maze were performed. Immunohistochemistry and western blotting were conducted. In the present results, treadmill exercise alleviated aggressive tendency and improved correct decision in the spatial learning memory in the autistic rats. Treadmill exercise increased neurogenesis and the expressions of reelin and its down-stream molecules, PI3K, p-Akt, and p-ERK1/2, in the hippocampus of the autistic rats. The present study showed that treadmill exercise ameliorated aggressive behavior and improved spatial learning memory through activation of reeling signaling pathway in the valproic acid-induced autistic rats.

Alcohol exposure induces depression-like behavior by decreasing hippocampal neuronal proliferation through inhibition of the BDNF-ERK pathway in gerbils

Abstract Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

Treadmill exercise ameliorates motor disturbance through inhibition of apoptosis in the cerebellum of valproic acid-induced autistic rat pups

Autism is a neurological disorder that occurs during childhood and is characterized by impairments in social interaction and communication, as well as restricted and repetitive behaviors. Abnormalities of the cerebellum in autism include Purkinje cell loss and motor disturbance. In the present study, we evaluated the effect of treadmill exercise on motor coordination and balance in correlation with reelin expression and the rate of apoptosis in the cerebellum of autistic rat pups. For the induction of the autism-like animal models, 400 mg/kg valproic acid was subcutaneously injected into rat pups on postnatal day 14. Rat pups in the exercise groups were forced to run on a treadmill for 30 min, once a day, five times a week for 4 weeks, starting on postnatal day 28. Motor coordination and balance, as measured using the rotarod test and vertical pole test, were affected by the induction of autism. By contrast, treadmill exercise ameliorated motor dysfunction in the autistic rat pups. The expression levels of reelin, GAD67 and cyclin D1 in the cerebellum of the autistic rat pups were decreased, while the expression levels of these molecules were increased in autistic rat pups who engaged in treadmill exercise. In the cerebellum of the autistic rat pups, Bcl-2 expression was decreased and Bax expression was increased. By contrast, treadmill exercise enhanced Bcl-2 expression and suppressed Bax expression. The therapeutic effect of treadmill exercise on motor deficits may be due to the reelin-mediated anti-apoptotic effect on cerebellar Purkinje neurons.

Treadmill exercise facilitates recovery of locomotor function through axonal regeneration following spinal cord injury in rats

Spinal cord injury (SCI) disrupts both axonal pathways and segmental spinal cord circuity, resulting in permanent neurological deficits. Physical exercise is known to increase the expression of neurotrophins for improving the injured spinal cord. In the present study, we investigated the effects of treadmill exercise on locomotor function in relation with brain-derived neurotrophic factor (BDNF) expression after SCI. The rats were divided into five groups: control group, sham operation group, sham operation and exercise group, SCI group, and SCI and exercise group. The laminectomy was performed at the T9–T10 level. The exposed dorsal surface of the spinal cord received contusion injury (10 g × 25 mm) using the impactor. Treadmill exercise was performed 6 days per a week for 6 weeks. In order to evaluate the locomotor function of animals, Basso-Beattie-Bresnahan (BBB) locomotor scale was conducted once a week for 6 weeks. We examined BDNF expression and axonal sprouting in the injury site of the spinal cord using Western blot analysis and immunofluorescence staining. SCI induced loss of locomotor function with decreased BDNF expression in the injury site. Treadmill exercise increased the score of BBB locomotor scale and reduced cavity formation in the injury site. BDNF expression and axonal sprouting within the trabecula were further facilitated by treadmill exercise in SCI-exposed rats. The present study provides the evidence that treadmill exercise may facilitate recovery of locomotor function through axonal regeneration via BDNF expression following SCI.

Treadmill exercise with bone marrow stromal cells transplantation potentiates recovery of locomotor function after spinal cord injury in rats

Transplantation of bone marrow stromal cells (BMSCs) is regarded as a promising candidate for the spinal cord injury (SCI). In the present study, we investigated whether treadmill exercise potentiate the effect of BM-SCs transplantation on the functional recovery in the SCI rats. The spinal cord contusion injury applied at the T9–T10 level using the impactor. Cultured BMSCs were transplanted into the lesion at 1 week after SCI induction. Treadmill exercise was conducted for 6 weeks. Basso-Beattie-Bresnahan (BBB) scale for locomotor function was determined. Sprouting axons in the lesion cavity were detected by immunofluorescence staining for neurofilament-200. Brain-derived neurotrophic factor (BDNF) and synapsin-I expressions were analyzed using western blotting. BMSCs transplantation improved BBB score and increased expressions of neurofilament-200, BDNF, and synapsin-I in the SCI rats. Treadmill exercise potentiated the improving effect of BMSCs transplantation on BBB score in the SCI rats. This potentiating effect of treadmill exercise could be ascribed to the enhancement of BDNF expression in the SCI rats.

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.

Effect of circuit training on body composition, physical fitness, and metabolic syndrome risk factors in obese female college students

The purpose of this study was to investigate the effect of a 12-week circuit training program on health-related physical fitness and metabolic syndrome risk factors in obese female college students. Twenty subjects with over 30% of accumulated body fat voluntarily participated and were randomly allocated to the control group (n=10) or circuit training group (n=10). The circuit training program consisted of 10 types of resistance and aerobic exercise and was performed 3 times per week for 12 weeks. Health-related physical fitness and metabolic syndrome risk factors were analyzed to elucidate the effect of the circuit training. Significant differences between groups were determined with two-way repeated analysis of variance and paired t-test. As a result of this study, body weight, % body fat, and body mass index in the circuit training group was significantly decreased compared to the control group. All health-related physical fitness indicators such as back strength, sit-up, sit-and-reach, and 1,600 m running time showed relative effects between groups or over time. Among the metabolic syndrome risk factors, waist measurement, triglyceride, and total cholesterol were significantly decreased but blood glucose, high-density lipo-protein cholesterol and low-density lipoprotein cholesterol did not show any significant difference. Therefore, the present data suggested that circuit training for 12 weeks may be effective in improving physical fitness and preventing metabolic diseases.

Effects of exercise on sexual function and central mechanism in the streptozotocin-induced diabetic rats

Diabetes mellitus is associated with the impairment of sexual function including desire and orgasmic dysfunction. Sexual dysfunction in the diabetes mellitus is due to a selective defect of the nitric oxide synthase (NOS) within paraventricular nucleus (PVN). c-Fos is an immediate early gene and c-Fos expression represents neuronal activity in response to various stimuli. In the present study, we investigated the effects of treadmill exercise on sexual behaviors and the expressions of NOS and c-Fos in the PVN were evaluated using streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by intraperitoneal injection of STZ. The rats in the treadmill exercise groups were made to run on a treadmill for 30 min once a day during 4 weeks. Male sexual behaviors were evaluated by recording the number of mounting, intromission, and ejaculation frequency. The present results revealed that treadmill exercise ameliorated sexual dysfunction in the STZ-induced diabetic rats. Treadmill exercise restored the contents of NOS and c-Fos in the PVN. The improving effect of treadmill exercise on sexual function can be considered as the neuronal activating effect of exercise through increasing expressions of NO and c-Fos.

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.