Search

Vascular dementia is the progressive change in blood vessels that leads to neuronal injuries in vulnerable areas induced by chronic cerebral hypoperfusion (CCH). CCH induces disruption of blood-brain barrier (BBB), and this BBB disruption can initiate the cognitive impairment and white matter injury. In the present study, we evaluated the effect of treadmill exercise on the cognitive impairment, white matter injury, and BBB disruption induced by CCH. Vascular dementia was induced by permanent bilateral common carotid arteries occlusion (BCCAO) in rats. The rats in the exercise group were made to run on a treadmill for 30min once a day for 14 weeks, starting 4 weeks after birth. Our results revealed that treadmill exercise group was alleviated the cognitive impairment and myelin degradation induced by CCH. The disruption of BBB after CCH indicates degradation of occludin, zonula occluden-1 (ZO-1), and up-regulation of matrix metalloproteinases (MMPs). Treadmill exercise may provide protective effects on BBB disruption from degradation of occludin, ZO-1, and overexpression of MMP-9 after CCH. These findings suggest that treadmill exercise ameliorates cognitive impairment and white matter injury from BBB disruption induced by CCH in rats. The present study will be valuable for means of prophylactic and therapeutic intervention for patients with CCH., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Dexmedetomidine (DEX), a selective α2 adrenergic agonist, is an anesthetic and sedative agent, and is reported to exert neuroprotective effects after hypoxic ischemia. However, there are few studies on the electrophysiological effect of DEX in hippocampal slices under ischemic conditions. The effects of DEX on field potential in hippocampal slices exposed to oxygen-glucose deprivation (OGD) were evaluated. Hippocampal slices were prepared from rats, and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded using the MED 64 system. Hypoxic-ischemia was induced by perfusion with glucose-free artificial cerebrospinal fluid (aCSF) bubbled with 95% N2 and 5% CO2, and hippocampal slices were perfused with DEX-added aCSF before, during, and after OGD induction. In the normal hippocampal slices, perfusion with 1 and 10μM DEX did not significantly decrease the normalized fEPSP amplitude, but 100μM DEX significantly reduced the fEPSP amplitude compared with its baseline control. The induction of OGD remarkably decreased the fEPSP amplitude, whereas the pre-, co-, and post-treatment of 10μM DEX gradually promoted recovery after washing out, and consequently the amplitude of fEPSP in DEX pre-, co-, and post-treated OGD slices were significantly higher than that in the untreated OGD slices at 10min and 60min after washing out. In particular, co-treatment with DEX conspicuously promoted the recovery of the fEPSP amplitude at the beginning of washing out. These results suggest the possibility of DEX as a therapeutic agent to prevent hypoxic-ischemic brain damage and promote functional recovery after ischemia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Brain inflammation plays a pivotal role in the pathogenesis of chronic neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. We investigated the effects of treadmill exercise and wheel exercise on spatial learning ability in relation with long-term potentiation (LTP) using lipopolysaccharide-induced brain inflammation in the rats. Brain inflammation was induced by an injection of LPS into the cerebral ventricle. We found that brain inflammation impaired spatial learning ability and suppressed the induction of LTP in the hippocampus, as well as weakening expressions of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (Trk-B) with the phosphorylated cyclic AMP response element binding protein (p-CREB). Both treadmill exercise and wheel exercise significantly improved spatial learning ability deteriorated by brain inflammation. These effects can be ascribed to the long-lasting effect of exercise on LTP through enhancement of the expressions regarding BDNF, TrkB, and p-CREB. Treadmill exercise and wheel exercise exerted similar effects on these factors. We infer that exercise may alleviate brain inflammation-induced learning impairment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder of cognition. Behavioral symptoms of ADHD are inattention, hyperactivity, and impulsivity. We investigated the effects of treadmill exercise and methylphenidate (MPH) on activity and spatial learning memory in relation to dopamine synthesis and brain-derived neurotrophic factor (BDNF) expression using spontaneously hypertensive adult male rats. The rats in the MPH-treated group received 1mg/kg MPH orally once a day for 28days. The rats in the treadmill exercise group were made to run on a treadmill for 30min once a day, five times a week, for 28days. Activity was determined by an open-field test and spatial learning memory was evaluated by an 8-arm maze test. Immunohistochemistry and Western blotting were conducted to examine the levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, and BDNF. The rats in the ADHD group showed hyperactivity and spatial learning memory deficit. Reduction of TH in the striatum and substantia nigra and BDNF in the hippocampus was observed of the rats in the ADHD group. Treadmill exercise and MPH alleviated the ADHD-induced hyperactivity and spatial learning memory impairment. Expressions of TH and BDNF in the ADHD rats were also increased by both treadmill exercise and MPH. These findings provide a possibility that exercise may be used as an effective therapeutic intervention for ADHD patients as MPH treatment., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Stressful experiences, such as an unsatisfactory mother-infant relationship after delivery, can induce depressive disorders, and it is well-known that stressors impair memory function. The hippocampus plays a crucial role in memory processes. In the present study, we determined whether a depressed-like state induced by repeated separation of pups affects the memory capability of the maternal rats. We also determined the effects of repeated separation from pups on cell proliferation, apoptosis, and serotonin expression in the brains of maternal rats. In the present results, the immobility time in the forced swim test was increased and the climbing time was decreased in the mothers separated from their pups. The latency in the step-down avoidance task was increased in the mothers separated from their pups. Also, the expressions of serotonin (5-hydroxytryptamine) and tryptophan hydroxylase in the dorsal raphe were decreased in the mothers separated from their pups. The number of Ki-67-positive cells was decreased, while the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hippocampal dentate gyrus was increased in the mothers separated from their pups. Based on the present results, it is suggested that separation of pups might induce a depressed-like state in the maternal rats with reduced cell proliferation and increased apoptosis in the hippocampus, resulting in memory impairment of maternal rats., ((c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Alzheimer's disease is a progressive neurodegenerative disease clinically characterized by dementia and neurobehavioral deterioration. Hippocampal neurons are vulnerable to injury induced by Alzheimer's disease. The immediate early gene c-Fos has been used as a marker of neuronal activity. In the present study, we investigated the effects of treadmill exercise on long-term memory capacity and c-Fos expression in the hippocampus of rats with Alzheimer's disease. The rat model of Alzheimer's disease used in the present study was induced by the intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise group were forced to run on a treadmill for 30 min once daily for 14 consecutive days starting at 3 days after the ICV injection of STZ. The results of the present study showed that ICV injection of STZ impaired long-term memory capacity and decreased the number of c-Fos-positive cells in several regions of the rat hippocampus. However, treadmill exercise alleviated long-term memory deficits and enhanced c-Fos expression in the rats with ICV injection of STZ. The results of the present study showed that treadmill exercise could be a useful strategy for treating several neurodegenerative diseases.

Paraplegia is one of the most common complications following aortic aneurysmal surgery. This study was designed to determine if isoflurane-induced delayed preconditioning is mediated by nuclear factor kappaB (NF-kappaB) in the rat spinal cord. The animals were divided into four groups: the control group, the pyrrolidinedithio carbamate (PDTC, an NF-kappaB inhibitor)-treated group, the isoflurane-treated group, and the PDTC/isoflurane-treated group. In the PDTC-treated groups, 2% 100mg/kg PDTC was administered intraperitoneally at 1h before operation and at 24h and 48 h after reperfusion. The rats in the isoflurane-treated groups received 30 min inhalation of 2.8% isoflurane at 24h before spinal cord ischemia. Pretreatment with NF-kappaB inhibitor significantly reduced NF-kappaB expression and the number of intact motor neurons when compared to the control group. Preconditioning with isoflurane increased the number of normal motor neurons, whereas pretreatment with both PDTC and isoflurane significantly decreased them, compared to the isoflurane-treated group. Isoflurane-induced delayed preconditioning on spinal cord ischemia improved histopathological outcomes. This neuroprotective effect of isoflurane preconditioning on spinal cord ischemia is associated with NF-kappaB expression.

Stress urinary incontinence leads to the involuntary loss of urine during abdominal strain caused by sneezing, laughing, and coughing. Acupuncture has been widely used for the treatment and prevention of a variety of diseases in traditional medicine. Acupuncture has also been used to relieve the symptoms of functional disorders of the lower urinary tract. In the present study, we investigated the effect of acupuncture at the Sanyinjiao (SP6) acupoint on stress urinary incontinence in rats. The present results showed that abdominal leak point pressure was decreased in rats with stress urinary incontinence, while acupuncture at the SP6 acupoint significantly enhanced the abdominal leak point pressure. The expression of c-Fos in the pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preoptic nucleus (MPA) regions was increased by the induction of stress urinary incontinence, and acupuncture at the SP6 acupoint significantly decreased c-Fos expression in these areas. In the present study, we showed that acupuncture has therapeutic effect on the symptoms of stress urinary incontinence, and this effect of acupuncture is associated with modulation of c-Fos expression in the brain.

In Parkinson's disease, the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra leads to debilitating motor dysfunction. In the present study, we investigated the effects of treadmill exercise on the dopaminergic neuronal cell death in the substantia nigra and on the dopaminergic fiber loss in the striatum of Parkinson's rats. Parkinson's rats were made by injecting 6-hydroxydopamine into the striatum with using a stereotaxic instrument. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days after 6-hydroxydopamine administration into the striatum. Two weeks after the intrastriatal injection of 6-hydroxydopamine, the rats without treadmill exercise displayed rotational asymmetry following injection of apomorphine (0.5 mg/kg, s.c.). In contrast, the rats undergoing treadmill exercise showed a significant reduction of rotational asymmetry. Analysis via immunohistochemistry for the tyrosine hydroxylase expression revealed a substantial loss of cell bodies in the substantia nigra and their projected fibers in the striatum ipsilateral to the lesion following 6-hydroxydapamine injection into the striatum. However, treadmill running enhanced the survival of dopaminergic neurons in the substantia nigra and also their fibers projecting into the striatum. The results of the present study show that treadmill exercise may provide therapeutic value for the treatment of Parkinson's disease patients.

In this study, we investigated the effect of acupuncture at the Zusanli acupoint (ST36) on the nigrostriatal dopaminergic neuronal cell death in the rats with Parkinson's disease. Two weeks after unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum, an apomorphine-induced rotational behavior test showed significant rotational asymmetry in the rats with Parkinson's disease. Immunostaining for tyrosine hydroxylase demonstrated a dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. Acupuncture at the ST36 for 14 days significantly inhibited rotational asymmetry in the rats with Parkinson's disease, and also protected against 6-OHDA-induced nigrostriatal dopaminergic neuronal loss. These effects of acupuncture were not observed for the non-acupoint (hip) acupuncture. The present study shows that acupuncture at the ST36 acupoint can be used as a useful strategy for the treatment of Parkinson's disease.

Melatonin has been reported to possess strong antioxidant actions, and is able to directly scavenge a variety of reactive oxygen species (ROS). The present study investigated whether melatonin possesses protective effects against Abeta-induced cytotoxicity in microglial cells. Cells treated with Abeta exhibited several characteristic features of apoptosis, while cells pre-treated with melatonin prior to exposure to Abeta showed a decrease in the occurrence of such apoptotic features. Several previous studies have demonstrated the involvement of ROS in Abeta-induced neurotoxicity, and ROS generated by Abeta have been reported to lead to the activation of nuclear factor-kappa B (NF-kappaB), a transcription factor; pre-treatment with melatonin in the present study reduced the level of Abeta-induced intracellular ROS generation, inhibited NF-kappaB activation, and suppressed the Abeta-induced increase in caspase-3 enzyme activity. In addition, it was found that pre-treatment with melatonin inhibits Abeta-induced increase in the levels of bax mRNA and that it enhances the level of bcl-2 expression. Based on these findings, the authors speculate that melatonin may provide an effective means of treatment for Alzheimer's disease through attenuation of Abeta-induced apoptosis.

Maternal alcohol consumption during pregnancy is known to have a detrimental effect on the development of the fetus and its central nervous system (CNS) in particular. In the present study, the dose-dependence of the effect of maternal alcohol on hippocampal c-Fos expression, which is a marker of hippocampal neuronal activity and which is induced by a variety of stimuli, was examined in infant rats. In the present study, it was shown that expression of c-Fos in the hippocampus is decreased following treatment with alcohol in a dose-dependent fashion. Based on the results of the present study and the findings of other studies, it can be suggested that suppression of c-Fos expression in the hippocampus of infant rats with maternal alcohol administration mediates the associated developmental retardation and/or anomalies.

In the present study, the effect of treadmill exercise on short-term memory, apoptotic neuronal cell death, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils was investigated. Step-down inhibitory avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 and 5-bromo-2'-deoxyuridine (BrdU) were used. Ischemia was induced by the occlusion of both common carotid arteries (CCA) of gerbils for 5 min. Gerbils in exercise groups were forced to run on a treadmill for 30 min once a day for 10 consecutive days. Such treadmill exercise improved short-term memory by suppressing the ischemia-induced apoptotic neuronal cell death in the dentate gyrus. In addition, treadmill running suppressed the ischemia-induced cell proliferation in the dentate gyrus. The present results suggest that treadmill exercise overcomes the ischemia-induced apoptotic neuronal cell death and thus facilitates the recovery following ischemic cerebral injury.

Intracerebral hemorrhage is one of the most devastating types of stroke. In the present study, the effect of acupuncture on intrastriatal hemorrhage-induced neuronal cell death in rats was investigated via Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and immunohistochemistry for caspase-3. The present results showed that lesion size and apoptotic neuronal cell death in the striatum were significantly increased following intrastriatal hemorrhage in rats and that acupunctural treatment at the Zusanli acupoint suppressed the hemorrhage-induced increase in lesion size and apoptotic neuronal cell death in the striatum. In the present study, it can be suggested that acupunctural treatment, especially at the Zusanli acupoint, may aid in the recovery following central nervous system sequellae following intracerebral hemorrhage., (Copyright 2004 Elsevier Ireland Ltd.)

In the present study, it was investigated whether 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA-AM), an intracellular Ca(2+) chelator, possesses protective effect against caffeine-induced apoptosis in the central nervous system. Through morphological and biochemical analyses, cells treated with caffeine exhibited several apoptotic features. On the other hand, cells treated with caffeine and BAPTA-AM, showed decreased occurrence of apoptotic features. In addition, it was shown that BAPTA-AM treatment inhibits caffeine-induced increase of caspase-3 enzyme activity. These results show that caffeine induces apoptotic death in human SK-N-MC neuroblastoma cells and BAPTA-AM prevents apoptosis by attenuating caffeine-induced caspase-3 activation.

The impact of age on the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats was investigated via 5-bromo-2'-deoxyuridine immunohistochemistry. Animals of different ages were used: 4-week-old, 8-week-old, and 62-week-old. Based upon the present study, the most prominent cell proliferation in the dentate gyrus was observed in the 4-week-old rats, and decreased in direct relation to the age of the animals. In addition, although treadmill exercise increased cell proliferation in the dentate gyrus of animals in all age groups, the most potent enhancing effect appeared in the 8-week-old rats. The present results demonstrate that age is an important factor in the regulation of cell proliferation in the dentate gyrus and that the enhancing effect of the treadmill exercise on cell proliferation also depends on age status.

Exercise is known to potentially affect the eating patterns. In the present study, the effect of treadmill exercise on the expressions of nitric oxide synthase (NOS) and neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) of food-deprived rats was investigated using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nNOS immunohistochemistry. The present results showed that food deprivation increased NOS and nNOS expressions in the PVN of the hypothalamus and treadmill exercise suppressed food deprivation-induced enhancing of NOS and nNOS expressions in the PVN. The most suppressive effect of treadmill exercise on the expressions of NOS and nNOS were observed in the heavy-intensity exercise group. Based on the present study, it is possible that treadmill exercise alleviates desire for food under food-deprivation conditions via modulation of NOS expression.

Intracerebral hemorrhage is one of the most devastating types of stroke. This disease is known to cause severe neurological damage and also has a very high mortality rate. In this study, the effect of treadmill exercise on intrastriatal hemorrhage-induced neuronal cell death was investigated. Intrastriatal hemorrhage was caused by injection of collagenase into the striatum using a stereotaxic instrument. Animals of the exercise group were made to run on a treadmill for 30 min once a day during 10 consecutive days. In the present results, treadmill exercise was shown to suppress the increase in the size of hemorrhage-induced lesions and the increase in caspase-3 expression in the striatum. Based on these results, it is possible that treadmill exercise aids in the recovery from central nervous system sequelae following intracerebral hemorrhage.

Uncaria rhynchophylla is a medicinal herb which has sedative and anticonvulsive effects and has been applied in the treatment of epilepsy in Oriental medicine. In this study, the effect of alkaloid fraction of U. rhynchophylla against N-methyl-D-aspartate (NMDA)-induced neuronal cell death was investigated. Pretreatment with an alkaloid fraction of U. rhynchophylla for 1 h decreased the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices and also inhibited NMDA-induced enhanced expressions of apoptosis-related genes such as c-jun, p53, and bax. In the present study, the alkaloid fraction of U. rhynchophylla was shown to have a protective property against NMDA-induced cytotoxicity by suppressing the NMDA-induced apoptosis in rat hippocampal slices.

Acupuncture has been used for the enhancement of functional recovery from various disorders including stroke. In the present study, the effects of acupuncture on the c-Fos expression and apoptosis in the hippocampal CA1 region of gerbils following transient global ischemia were investigated via immunohistochemistry for c-Fos and caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Enhanced Fos, TUNEL, and caspase-3 positivities were detected in the hippocampal CA1 region in the ischemic gerbils. Acupunctural treatment suppressed the ischemia-induced increment in the number of Fos-, TUNEL-, and caspase-3-positive cells: the most potent suppressive effect was observed at the Zusanli acupoint. These results suggest that acupunctural treatment alleviates ischemia-induced apoptosis and may aid in the recovery following ischemic cerebral injury.

Diabetes mellitus is a metabolic disorder with serious sequelae in humans. Hyperphagia is a characteristic symptom of diabetes and is a central nervous system-mediated disorder. Neuropeptide Y (NPY) is a 36-amino-acid peptide and is concentrated in the hypothalamus which is an appetite-regulating area. NPY is known to stimulate appetite and decrease energy expenditure. In the present study, the effect of treadmill exercise on the hypothalamic NPY expression in rats with streptozotocin (STZ)-induced diabetes was investigated via immunohistochemistry. Enhanced NPY expression in the paraventricular nucleus and arcuate nucleus was observed in the STZ-induced diabetic rats. Treadmill exercise suppressed a diabetes-induced increase of NPY expression. The present results suggest the possibility that treadmill exercise inhibits diabetes-induced increment of the desire for food.

Bupivacaine and ropivacaine are local surgical anesthetics with great efficacy in post-operative pain relief and labor analgesia. In the present study, the effects of bupivacaine and ropivacaine on ion currents induced by glycine and glutamate in acutely dissociated hippocampal CA1 neurons of rats were investigated via a nystatin-perforated patch clamping method at a clamped voltage. The magnitude of the glycine-induced ion currents was decreased reversibly and in a time-dependent manner by continuous application of 0.1 mg/ml of either bupivacaine or ropivacaine. The magnitude of the glutamate-induced ion currents was also suppressed time-dependently by continuous application of either bupivacaine or ropivacaine. The inhibitory action of bupivacaine and ropivacaine on currents induced by glycine and glutamate could be one of the mechanisms behind the actions of these anesthetics.

Acupuncture has been used as a clinical treatment in Oriental medicine for various diseases including diabetes mellitus, one of the most common metabolic disorders in humans. In the present study, the effect of acupuncture on the expressions of neuronal nitric oxide synthase (nNOS) and nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (DL-PAG) area of rats with streptozotocin (STZ)-induced diabetes was investigated via nNOS immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. Enhanced expression of nNOS and NOS was detected in the DL-PAG of rats with STZ-induced diabetes, and acupunctural treatment at Zusanli acupoint suppressed the diabetes-induced enhancement in the expression of nNOS and NOS. The present results demonstrate that acupuncture is effective in the modulation of the expression of nNOS and NOS in the DL-PAG under diabetic conditions.

The effects of treadmill exercise and swimming on cell proliferation in the dentate gyrus and the involvement of opioid receptors were investigated via 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. Sprague-Dawley rats of the running groups were made to run on treadmill for 30 min each day, while those of the swimming groups were made to swim for 5 min each day over 3 consecutive days. In addition, intensity-dependency of the effects of running and swimming on cell proliferation was investigated. The present results demonstrate that both treadmill running and swimming increase the number of BrdU-labeled cells in the dentate gyrus and these increasing effects are more potent in light intensity and 5 min swimming groups. Treatment with naloxone increases cell proliferation in the dentate gyrus in all groups, although this increase is statistically insignificant.

In the present study, the effects of acupuncture on the endurance treadmill exercise, serotonin (5-hydroxytryptamine, 5-HT) synthesis, and tryptophan hydroxylase (TPH) expression in the dorsal raphe nuclei were investigated. Acupunctural stimulation were bilaterally inserted into the locus of Zusanli in each hind leg for 20 min. Onset of exhaustion time on the treadmill running was increased significantly by acupunctural stimulation and exercise-induced increments of the 5-HT synthesis and TPH expression in the dorsal raphe were suppressed by acupunctural stimulation. Based on the results, it can be suggested that the suppressive effects of acupunctural stimulation on the 5-HT synthesis and TPH expression in the dorsal raphe during exercise is one of ergogenic mechanisms of acupuncture.

The medicinal plant Hypericum perforatum Linn, commonly known as St. John's wort, has been used as an antidepressant. To investigate whether St. John's wort possesses a protective effect against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in neuronal cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, flow cytometry analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with H(2)O(2) exhibited several apoptotic features, while those pre-treated with St. John's wort prior to H(2)O(2) exposure showed a decreased occurrence of apoptotic features. In addition, pre-treatment with St. John's wort inhibited H(2)O(2)-induced increase in caspase-3 enzyme activity. These results suggest that St. John's wort may exert a protective effect against H(2)O(2)-induced apoptosis in human neuroblastoma cells., (Copyright 2002 Elsevier Science Ireland Ltd.)

Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of various neuropsychiatric disorders. In the present study, the effects of alcohol and nicotine on the synthesis of 5-HT and the expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT synthesis, in the dorsal and median raphe of young rats were investigated via immunohistochemistry. The numbers of the 5-HT-positive and TPH-positive cells were reduced by alcohol and nicotine treatment in a dose-dependent manner. Based on the results, it can be suggested that the pathogenesis of alcohol- and nicotine-induced neuropsychological disorders involves alcohol- and nicotine-induced suppression of 5-HT synthesis and TPH expression in raphe, and that this may be of particular relevance in the consumption of alcohol and nicotine during adolescence., (Copyright 2002 Elsevier Science Ireland Ltd.)

In the present study, the effects of cold-water immersion on cell proliferation and nitric oxide synthase expression in the dentate gyrus of rats were investigated. Sprague-Dawley rats were divided into four groups: the control-rest group; the control-heat group; the cold-rest group; and the cold-heat group. Cold-water immersion for 5 min at 4 degrees C suppressed the numbers of 5-bromo-2'-deoxyuridine-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive cells in the dentate gyrus, and these numbers were increased by warming for 30 min at 30 degrees C. In the present study, it was demonstrated that warming protects against cold stress-induced suppression of new cell formation, and results suggest that nitric oxide, the synthesis of which is affected adversely by cold-water immersion, may play an important role in the regulation of cell proliferation., (Copyright 2002 Elsevier Science Ireland Ltd.)

In this study, effects of acupuncture at Zusanli acupoint on cell proliferation and expression of neuropeptide Y (NPY) in the dentate gyrus (DG) of streptozotocin-induced diabetic rats were investigated. Sprague-Dawley rats were divided into six groups: the control group, the non-diabetic and Zusanli-acupunctured group, the non-diabetic and non-acupoint-acupunctured group, the streptozotocin-induced-diabetes group, the streptozotocin-induced-diabetes and Zusanli-acupunctured group, and the streptozotocin-induced-diabetes and non-acupoint-acupunctured group. In the streptozotocin-induced diabetes group, the mean 5-bromo-2'-deoxyuridine-positive and NPY-positive cell counts in the DG were significantly decreased compared to the control group. Stimulation of the Zusanli resulted in increased cell proliferation and neuropeptide Y levels in the diabetic group. In the present results, it can be suggested that acupuncture may affect cell proliferation in the DG of streptozotocin-induced diabetic rats by regulating neuropeptide Y expression.

Effect of nicotine on nitric oxide synthase (NOS) expression in various hypothalamic regions was investigated in rats via nicotineamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Sprague-Dawley rats were divided into the fed group, the fed and nicotine-treated group, the food-deprived group, and the food-deprived and nicotine-treated group. The fed groups received abundant food and water, while food was withheld from the food-deprived groups for 48 h. The nicotine-treated groups were injected with nicotine. Following food deprivation, enhanced NAPDH-d expression was detected in the paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area of the hypothalamus. Nicotine administration to the food-deprived rats resulted in decreased NADPH-d positivity. The present results indicate that nicotine administration is effective in limiting the enhancement in NOS expression following food restriction.

Effect of caffeine on the expression of tryptophan hydroxylase (TPH), rate limiting enzyme of serotonin synthesis, in dorsal and median raphe was investigated via immunohistochemistry. In exercise groups, Sprague-Dawley rats were put on treadmill running for 30 min per day for 6 consecutive days. On the seventh day, animals of control-with-caffeine group were injected subcutaneously with 4 mg/kg caffeine, while control-without-caffeine group were injected with 0.9% NaCl, sacrificed 2 h later. Exercise-with-caffeine group and exercise-without-caffeine group were injected with caffeine and NaCl, respectively; all-out time was determined 1 h after injection, and then sacrificed. Caffeine increased all-out time in exercised rats, and inhibited the exercise-induced elevation in TPH expression. The suppressive effect of caffeine on TPH expression in exercised rats can be suggested as one possible ergogenic mechanism of caffeine.

The aim of the present study was to investigate whether stimulation of auricular acupuncture point has any effects on the expression of neuropeptide Y (NPY), appetite-inducing factor particularly abundant in the mammalian hypothalamus. In food-deprived condition, enhanced NPY expression was detected in both the arcuate nucleus (ARN) and the paraventricular nucleus (PVN) of the hypothalamus via immunohistochemistry in Sprague-Dawley rats. Needling the unfed rats on the auricular point resulted in decreased NPY levels in both the ARN and PVN, while it increased NPY levels in the ARN and PVN of fed rats. The present findings indicate that auricular acupuncture may affect NPY expression in the ARN and PVN of the hypothalamus.

The homozygous anorexia mutant (anx/anx) mice present with premature death during the third or fourth postnatal week: this phenotype is caused by a lethal mutation, anx, on chromosome 2, which has an autosomal recessive mode of inheritance. These animals also present phenotypically with decreased food intake, weight loss, and neurological deficits such as hyperactivity, body tremors, uncoordinated gait, and head weaving. In order to investigate changes in the occurrence of cell proliferation and apoptosis in the dentate gyrus of the hippocampus of anx/anx mice, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay were performed in this study. In addition, the volume of the dentate gyrus was estimated via stereological analysis. anx/anx mice showed significantly higher numbers of both BrdU- and TUNEL-positive cells in the dentate gyrus than those of the control mice. Furthermore, the volume of the dentate gyrus of anx/anx mice was significantly reduced compared to that of the control mice.

The effects of acupuncture on cell proliferation in the dentate gyrus of gerbils after transient global ischemia were investigated in this study. Acupuncture was performed on Zusanli (ST36), which is a well known acupoint in animals and humans. In Oriental medicine, Zusanli has been commonly used for the enhancement of functional recovery in stroke patients. Through 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, an increase in cell birth in the dentate gyrus of gerbils after ischemic injury was detected. Interestingly, acupunctural treatment in ischemic gerbils resulted in a significant increase in the number of BrdU-positive cells in the dentate gyrus. The present findings indicate that acupuncture may affect cell proliferation in the dentate gyrus of gerbils after ischemic injury.

Expression of ciliary neurotrophic factor (CNTF) was observed in reactive astrocytes in injured spinal cord of the adult rat. After unilateral incision of the dorsal funiculus at a midthoracic level, the rats were sacrificed on the day of postoperation (DPO) 3, 7, 14 or 28. Western blot analysis of spinal cord extracts showed that the intensity of the CNTF-immunoreactive band of 24 kDa was increased on DPO 3 and 7 and decreased on DPO 14. CNTF- or glial fibrillary acidic protein (GFAP)-like immunoreactivity was also increased progressively in the injured dorsal funiculus and adjacent gray matter. Double immunofluorescence histochemistry revealed that all CNTF-like immunoreactive cells showed GFAP-like immunoreactivity. The CNTF upregulation in the reactive astrocytes may play important roles in repair process after spinal cord injury.