Seung-Soo Baek

Treadmill exercise prevents aging-induced failure of memory through an increase in neurogenesis and suppression of apoptosis in rat hippocampus

Aging leads to functional changes in the hippocampus, and consequently induces cognitive deficits, such as failure of memory. Neurogenesis in the hippocampal dentate gyrus continues throughout life, but steadily declines from early adulthood. Apoptosis occurs under various pathologic and physiologic conditions, and excessive apoptotic cell death can cause a number of functional disorders in humans. Apoptosis in the hippocampus also disturbs cognitive functions. In this study, we examined the effect of treadmill exercise on memory in relation to neurogensis and apoptosis in the hippocampal dentate gyrus of old-aged rats. The present results showed that loss of memory by aging was associated with a decrease in neurogenesis and an increase in apoptosis in the hippocampal dentate gyrus. Treadmill exercise improved short-term and spatial memories by enhancing neurogenesis and suppressing apoptosis in the hippocampal dentate gyrus of old-aged rats. In the present study, we showed that treadmill exercise is a very useful strategy for preventing failure of memory in the elderly.

Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis

Traumatic brain injury (TBI) occurs when an outside force impacts the brain. The main problem associated with TBI is neuronal cell death of the brain, and the outcome of TBI ranges from complete recovery to permanent disability, and sometimes death. Physical exercise is known to ameliorate neurologic impairment induced by various brain insults. In the present study, we investigated the effects of treadmill exercise on short-term memory and apoptosis in the hippocampus following TBI in rats. TBI was induced by an electromagnetic-controlled cortical impact. The rats in the exercise group were forced to run on a treadmill for 30min once daily for 10 consecutive days, beginning 2days after induction of TBI. For the current study, a step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, Western blot for Bcl-2 and Bax, and immunohistochemistry for caspase-3 were conducted. The present results revealed that TBI impaired short-term memory, and increased DNA fragmentation and caspase-3 expression in the hippocampus. Induction of TBI also enhanced expression of pro-apoptotic factor Bax protein and suppressed expression of anti-apoptotic factor Bcl-2 protein in the hippocampus. Treadmill exercise alleviated short-term memory impairment, and decreased DNA fragmentation and caspase-3 expression in the hippocampus. In addition, treadmill exercise remarkably suppressed expression of Bax protein and slightly increased expression of Bcl-2 protein in TBI-induced rats. The present study showed that treadmill exercise might overcome TBI-induced apoptotic neuronal cell death, thus facilitating recovery following TBI.

Effects of postnatal treadmill exercise on apoptotic neuronal cell death and cell proliferation of maternal-separated rat pups.

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and they can eventually cause memory impairment. In this study, we investigated the effects of postnatal treadmill exercise on the long-term memory capability, spatial learning ability, and depressive state, on the 5-hydroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the dorsal raphe nuclei, and on the apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. The rat pups in the maternal separation groups were separated from their respective mothers on the postnatal day 14. The rat pups in the maternal separation group showed depressive state with deceased memory capability and learning ability compared to the rat pups in the maternal care group. Postnatal treadmill exercise increased memory capability and learning ability and alleviated depressive state of the rat pups in the maternal separation group. The 5-HT synthesis and TPH expression in the dorsal raphe nuclei and cell proliferation in the hippocampal dentate gyrus were significantly decreased in the maternal-separated rat pups, and postnatal treadmill exercise increased 5-HT synthesis, the TPH expression, and the cell proliferation. In contrast, apoptotic neuronal cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and postnatal treadmill exercise suppressed the maternal separation-induced apoptosis. The present results demonstrated that postnatal treadmill exercise alleviated maternal separation-induced depression with decrease of memory capability and learning ability, by suppressing apoptotic neuronal cell death and by enhancing cell proliferation.

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.

Treadmill Exercise Ameliorates Short-Term Memory Disturbance in Scopolamine-Induced Amnesia Rats

Purpose Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. Methods To induce amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once per day for 14 days. A step-down avoidance test for short-term memory was conducted. AChE histochemistry, immunohistochemistry for collagen IV, and doublecortin were performed. Results Short-term memory deteriorated in the mice with scopolamine-induced amnesia, concomitant with enhanced AChE expression and suppression of angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short-term memory impairment, suppressed AChE expression, and enhanced angiogenesis in the mice with scopolamine-induced amnesia. Conclusions Overexpression of AChE is implicated in both brain and renal disease. The findings of our study indicate that treadmill exercise may be of therapeutic value in neurodegenerative and renal diseases by suppressing the effects of AChE expression.

Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats

Alzheimer’s disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer’s disease.

Role of exercise on the brain

The functions of adult hippocampal neurogenesis have been extensively investigated during the past decade. Numerous studies have shown that adult neurogenesis may play an important role in the hippocampal-dependent learning and memory. This study evaluated the influence of exercise on hippocampal neurogenesis, neural plasticity, neurotrophic factors, and cognition. Areas of research focused on enhancing effect of exercise for adult hippocampal neurogenesis and protective role of exercise against brain diseases. The present study suggests that exercise improves brain functions and prevents decline of cognition across the lifespan. Understanding of neurobiological mechanisms of exercise on brain functions may lead to the development of novel therapeutic strategy for neurodegenerative disorders.

Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats

Alzheimer disease (AD) is a most common form of dementia and eventually causes impairments of learning ability and memory function. In the present study, we investigated the effects of treadmill exercise on the symptoms of AD focusing on the microglial activation-induced apoptosis. AD was made by bilateral intracerebroventricular injection of streptozotocin. The rats in the exercise groups were made to run on a treadmill once a day for 30 min during 4 weeks. The distance and latency in the Morris water maze task and the latency in the step-down avoidance task were increased in the AD rats, in contrast, treadmill exercise shortened these parameters. The numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive and caspase-3-positive cells in the hippocampal dentate gyrus were decreased in the AD rats, in contrast, treadmill exercise suppressed these numbers. Expressions of glial fibrillary acidic protein (GFAP) and cluster of differentiation molecule 11B (CD11b) in the hippocampal dentate gyrus were increased in the AD rats, in contrast, treadmill exercise suppressed GFAP and CD11b expressions. Bax expression was increased and Bcl-2 expression was decreased in the hippocampus of AD rats, in contrast, treadmill exercise decreased Bax expression and increased Bcl-2 expression. The present results demonstrated that treadmill exercise ameliorated AD-induced impairments of spatial learning ability and short-term memory through suppressing apoptosis. The antiapoptotic effect of treadmill exercise might be ascribed to the inhibitory effect of treadmill exercise on microglial activation.

Effect of treadmill exercise on social interaction and tyrosine hydroxylase expression in the attention-deficit/ hyperactivity disorder rats.

Attention-deficit/hyperactivity disorder (ADHD) involves clinically heterogeneous dysfunctions of sustained attention, with behavioral hyper-activity and impulsivity. The exact underlying mechanisms of ADHD are not known, however, impairment of dopaminergic system in the nigrostriatal pathway was suggested as the one of the possible mechanisms of ADHD. Tyrosine hydroxylase (TH) is the rate-limiting enzyme that is involved in the synthesis of dopamine. Spontaneous hypertensive rats have been used as the animal model for ADHD. Physical exercise is known to restore the brain functions disrupted by several neurode-generative and psychiatric disorders. In the present study, we investigated whether treadmill exercise exerts therapeutic effect on ADHD. Social interaction test for the evaluation of impulsivity was performed using spontaneous hypertensive rats. TH expressions in the substantia nigra and striatum were evaluated by immunohistochemistry. In the present results, the rats of ADHD model showed hyper-social behaviors. TH expressions in the substantia nigra and striatum were decreased in the rats of ADHD model. Treadmill exercise alleviated hyper-social behaviors in the ADHD rats. TH expressions of ADHD rats were also enhanced by treadmill exercise. Here in this study, we showed that treadmill exercise effectively alleviates the ADHD-induced symptoms through enhancing of TH expression in the brain.

Role of exercise on molecular mechanisms in the regulation of antidepressant effects

Regular exercise reduces depressive-like behavior activation. In this study, we look for exact roles of exercise on molecular and neuronal mechanisms for antidepressant action by studying the hippocampal neuroplasticity and proliferation. Increased hippocampal neurogenesis with exercise has potential significance for depression. Exercise promotes brain health in the molecular levels in the hippocampus and also affects behavior in a similar way to chronic antidepressant treatment. Wingless (Wnt) and frizzled signaling system plays an important role in cell proliferation, growth, and differentiation during development. Our results demonstrate complicated, differential effects of antidepressants on Wnt signaling system, and assume a role for selected signaling molecules in the neurogenic activity of antidepressant care. Our review suggests that exercise may preserve brain function by increasing neurogenesis through activating Wnt signaling pathway in the psychiatric disorders, such as depression.