Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice
Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice
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DOI：
10.1016/j.lfs.2012.10.003
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发表时间：
2012-12-17
期刊：
影响因子：
6.1
通讯作者：
Cho, Han-Jin
中科院分区：
文献类型：
--
作者：
Sung, Yun-Hee;Kim, Shin-Chul;Cho, Han-Jin
目的：帕金森病是一种以多巴胺能神经元逐渐丧失为特征的衰弱性神经退行性疾病。采用1-甲基-4-苯基-1，2，3，6-四氢吡啶/丙磺舒（MPTP/P）诱导的帕金森病小鼠模型，研究跑台运动对多巴胺能神经元丢失和小胶质细胞活化的影响。运动平衡和协调采用旋转杆试验。诱导型一氧化氮合酶（iNOS）和磷酸化细胞外信号调节激酶（p-ERK）、磷酸化氨基末端激酶（p-JNK）的表达。磷酸化p-38（p-p38）。免疫印迹法检测CD 200、CD 200受体。酪氨酸羟化酶（TH）和CD 11b的表达进行了评估，通过免疫组化。关键发现：帕金森病小鼠表现出不良的运动平衡和协调与黑质纹状体多巴胺能神经元的损失。在帕金森病小鼠中，iNOS表达通过磷酸化促分裂原活化蛋白激酶（p-MAPK）信号传导如p-ERK、p-JNK和p-p-38的上调而增强。在帕金森病小鼠中也观察到小胶质细胞活化，显示出CD 11b表达增加，CD 200和CD 200受体表达受到抑制。跑台运动可防止帕金森病小鼠黑质纹状体多巴胺能神经元的丢失，并改善运动平衡和协调功能障碍。跑步机运动抑制iNOS的表达通过下调MAPKs，也抑制小胶质细胞活化在帕金森氏症mice.Significance：跑步机运动通过抑制小胶质细胞活化在帕金森氏症小鼠抑制脑炎症，防止多巴胺能神经元的损失。(C)2012 Elsevier Inc. All rights reserved.
Aims: Parkinson's 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 Parkinson's disease mice.Main methods: Parkinson's disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30 min/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 NH2-terminal kinase (p-JNK). phosphotylated 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: Parkinson's 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 Parkinson's disease mice. Microglial activation was also observed in the Parkinson's 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 Parkinson's disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinson's disease mice.Significance: Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinson's disease mice. (C) 2012 Elsevier Inc. All rights reserved.