Baek-Vin Lim

Treadmill exercise ameliorates symptoms of methimazole-induced hypothyroidism through enhancing neurogenesis and suppressing apoptosis in the hippocampus of rat pups.

Thyroid hormones play a crucial role in new neuron production and maturation during brain development. Physical exercise is known to promote cell survival and functional recovery after brain injuries. In the present study, we investigated the effects of treadmill exercise on short‐term memory, spatial learning ability, neurogenesis, and apoptosis in hypothyroidism rat pups. On the 14th perinatal day, the pregnant rats were divided into two groups: the maternal control group and the maternal methimazole (MMI)‐treated group. For the induction of hypothyroidism in rat pups, MMI was added to the drinking water (0.02%, wt/vol), from the 14th prenatal day to the 49th postnatal day. After delivery, the male rat pups born from the maternal control group were assigned into the control group and the control and exercise group. The rat pups born from the maternal MMI‐treated group were divided into the hypothyroidism‐induction group and the hypothyroidism‐induction and treadmill exercise group. The rat pups in the exercise groups were forced to run on a motorized treadmill for 30 min once a day, starting on the 22nd postnatal day for 4 weeks. Induction of hypothyroidism during the fetal and early postnatal period showed suppression of neurogenesis and enhancement of apoptosis in the hippocampus. Short‐term memory and spatial learning ability were deteriorated in the hypothyroidism rat pups. Treadmill exercise during the postnatal period increased neurogenesis and inhibited apoptosis, and resulted in the improvement of short‐term memory and spatial learning ability in the hypothyroidism rat pups.

Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson’s rats

Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson’s disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson’s rats. Parkinson’s rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson’s rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson’s disease.

Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats

Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2′-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity.

Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats

Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation.

Treadmill exercise inhibits apoptotic neuronal cell death with suppressed vascular endothelial growth factor expression in the retinas of the diabetic rats

Diabetic retinopathy is one of the most important microvascular complications in diabetes, and it is the major cause of visual loss. Physical exercise is known to ameliorate the symptoms of metabolic syndromes such as diabetic mellitus. In the present study, we investigated the effects of treadmill exercise on vascular endothelial growth factor (VEGF) expression and apoptotic cell death in the retinas of streptozotocin (STZ)-induced diabetic rats. The male Sprague-Dawley rats were randomly divided into three groups (n = 10 in each group): control group, STZ-induce diabetes group, STZ-induced diabetes and treadmill exercise group. To induce diabetes in the experimental animals, a single intraperitioneal injection of STZ (50 mg/kg) was given to each animal. The rats in the exercise group were forced to run on a motorized treadmill for 30 min once a day during 1 week starting 6 weeks after STZ injection. In the present results, VEGF expression in the retinas was increased by induction of diabetes. The numbers of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the retinas were also enhanced by induction of diabetes. Treadmill exercise significantly decreased VEGF expression and suppressed the number of TUNEL-positive and caspase-3-positive cells in the retinas of diabetic rats. In the present study, we have shown that treadmill exercise might alleviate the progression of diabetic retinopathy through suppressing VEGF expression and apoptotic cell death in the retinas of the diabetic rats.

Treadmill exercise alleviates chronic mild stress-induced depression in rats

Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2′-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression.

Treadmill exercise prevents GABAergic neuronal loss with suppression of neuronal activation in the pilocarpine-induced epileptic rats

Epilepsy is a common neurological disorder characterized by seizure and loss of neuronal cells by abnormal rhythmic firing of neurons in the brain. In the present study, we investigated the effect of treadmill exercise on gamma-aminobutyric acid (GABA)ergic neuronal loss in relation with neuronal activation using pilocarpine-induced epileptic rats. The rats were divided into four groups: control group, control and treadmill exercise group, pilocarpine-induced epilepsy group, and pilocarpine-induced epilepsy and treadmill exercise group. Epilepsy was induced by intraperitoneal injection of 320 mg/kg pilocarpine hydrochloride. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 2 weeks. In the present results, neuronal loss in the hippocampal CA1 region was increased after pilocarpine-induced seizure. Treadmill exercise inhibited hippocampal neuronal loss in the epileptic rats. Glutamic acid decarboxylase (GAD67) expression in the hippocampal CA1 region was reduced by pilocarpine-induced seizure. Treadmill exercise increased GAD67 expression in the epileptic rats. c-Fos expression in the hippocampal CA1 region was increased in response to epileptic seizure. Treadmill exercise inhibited c-Fos expression in the epileptic rats. Epileptic seizure increased brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) expressions in the hippocampus. Treadmill exercise suppressed BDNF and TrkB expressions in the epileptic rats. In the present study, treadmill exercise prevented GABAergic neuronal loss and inhibited neuronal activation in the hippocampal CA1 region through the down-regulation of BDNF-TrkB signaling pathway.

Treadmill exercise alleviates depressive symptoms in rotenone-induced Parkinson disease rats

Parkinson disease (PD) is characterized by selective loss of the dopaminergic neurons. The symptoms of depression following PD are closely associated with reduced activity of the serotonergic system in the dorsal raphe. We explored the antidepressive effect of exercise and its possible mechanism using the rotenone-induced PD rats. PD rats were induced by subcutaneously injection with rotenone for 14 days. The rats in the exercise groups were made to run on a treadmill for 30 min once a day during 14 consecutive days. Forced swimming test, immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT), tryptophan hydroxylase (TPH), and western blot for serotonin 1A (5-HT1A) receptor were conducted. Injection of rotenone induced PD rats. PD rats showed depressive state and treadmill exercise ameliorated this depressive state. 5-HT, TPH, and 5-HT1A receptor expressions in the dorsal raphe were suppressed by rotenone injection and treadmill exercise increased the expressions of 5-HT, TPH, and 5-HT1A receptor in the rotenone-injected rats. The present results show that treadmill exercise ameliorated depressive symptoms in the rotenone-induced PD rats. The antidepressive effect of treadmill exercise might be ascribed to the enhancement of serotonergic function through upregulation of 5-HT1A expression in the dorsal raphe.

Treadmill exercise alleviates nigrostriatal dopaminergic loss of neurons and fibers in rotenone-induced Parkinson rats

Parkinson disease is one of the common brain diseases caused by dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. In the present study, the effects of treadmill exercise on motor performance, dopaminergic loss of neurons and fibers, and α-synuclein expression in the nigrostriatum were evaluated using rotenone-induced Parkinson rats. For the induction of Parkinson rats, 3-mg/kg rotenone was injected, once a day for 14 consecutive days. Treadmill running was conducted for 30 min once a day during 14 consecutive days. Rota-rod test for motor balance and coordination and immunohistochemistry for tyrosine hydroxylase and α-synuclein in the nigrostriatum were performed. In the present study, motor balance and coordination was disturbed by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated motor dysfunction in the rotenone-induced Parkinson rats. Nigrostriatal dopaminergic loss of neurons and fibers was occurred by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated nigrostriatal dopaminergic loss of neurons and fibers in the rotenone-induced Parkinson rats. α-Synuclein expression in the nigrostriatum was enhanced by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise suppressed α-synuclein expression in the rotenone-induced Parkinson rats. Treadmill exercise improved motor function through preservation of nigrostriatal dopaminergic neurons and fibers and suppression of nigrostriatal formation of Lewy bodies in rotenone-induced Parkinson rats.

Effects of amygdalin on the functional recovery and c-Fos expression in the ventrolateral periaqueductal gray region after sciatic crushed nerve injury in rats

Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. The expression of c-Fos is sometimes used as a marker of increased neuronal activity. We have prepared the aqueous extract of amygdalin from Armeniacae semen for pain control. In the present study, we investigated the effects of amygdalin on the recovery rate of the locomotor function and on the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used in this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Amygdalin enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. The present our study indicated that amygdalin activates neurons in the vlPAG, and it facilitates functional recovery following peripheral nerve injury.