Mal Soon Shin

Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice.

AIMS Parkinsons disease is a debilitating neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. We investigated the effects of treadmill exercise on dopaminergic neuronal loss and microglial activation using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P)-induced Parkinsons disease mice. MAIN METHODS Parkinsons disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30min/day, five times per week for four weeks. Motor balance and coordination was measured using rota-rod test. Expressions of inducible nitric oxide synthase (iNOS) and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated NH(2)-terminal kinase (p-JNK), phosphorylated p-38 (p-p38), CD200, and CD200 receptor were determined by western blotting. Expressions of tyrosine hydroxylase (TH) and CD11b were evaluated by immunohistochemistry. KEY FINDINGS Parkinsons disease mice displayed poor motor balance and coordination with loss of nigrostriatal dopaminergic neurons. iNOS expression was enhanced via up-regulation of phosphorylated mitogen-activated protein kinases (p-MAPKs) signaling, such as p-ERK, p-JNK, and p-p-38 in the Parkinsons disease mice. Microglial activation was also observed in the Parkinsons disease mice, showing increased CD11b expression with suppressed CD200 and CD200 receptor expressions. Treadmill exercise prevented the loss of nigrostriatal dopaminergic neurons, and ameliorated the motor balance and coordination dysfunction in the Parkinsons disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinsons disease mice. SIGNIFICANCE Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinsons disease mice.

Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin.

Alzheimers disease is a progressive neurodegenerative disease clinically characterized by dementia and neurobehavioral deterioration. Hippocampal neurons are vulnerable to injury induced by Alzheimers 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 Alzheimers disease. The rat model of Alzheimers 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.

Acupuncture suppresses ischemia-induced increase in c-Fos expression and apoptosis in the hippocampal CA1 region in gerbils.

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.

Treadmill exercise decreases intrastriatal hemorrhage-induced neuronal cell death via suppression on caspase-3 expression in rats

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.

Caffeine inhibits exercise-induced increase in tryptophan hydroxylase expression in dorsal and median raphe of Sprague-Dawley rats.

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.

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway.

Purpose Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. Methods Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. Results Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. Conclusions Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

Acupuncture suppresses intrastriatal hemorrhage-induced apoptotic neuronal cell death in rats.

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.

Administration of Ginseng radix Decreases Nitric Oxide Synthase Expression in the Hippocampus of Streptozotocin-Induced Diabetic Rats

Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). Alternation of NOS expression is implicated in the pathogenesis of numerous secondary complications of diabetes. Aqueous extract of Ginseng radix has traditionally been used for the various disorders including diabetes. In this study, the effect of Ginseng radix on the NOS expression in the hippocampus of streptozotocin (STZ)-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NOS expression was detected in the hippocampus of diabetic rats and administration of Ginseng radix suppressed NOS expression. Ginseng radix may aid the treatment of central nervous system complications in diabetes.

Treadmill exercise suppresses diabetes-induced increment of neuropeptide Y expression in the hypothalamus of rats

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.

Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils

Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a step-down avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, western blot analysis for B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax), immunohistochemistry for caspase-3 and immunofluorescence for 5-bromo-2′-deoxyuridine. The numbers of TUNEL-positive and caspase-3-positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl-2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemia-induced apoptosis by suppressing apoptosis-associated molecules, and thus ameliorated ischemia-induced short-term memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke.