تمرین بر روی دستگاه نوارگردان آنتی اکسیدان Nrf2 را برای محافظت از سلول های عصبی دوپامینرژیک nigrostriatal از صدمات +MPP فعال می کند (مقاله لاتین)

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Yi-Hsien Tsou a, Ching-Ting Shih a, Cheng-Hsin Ching a, Jui-Yen Huang a, Chauying J. Jen a, Lung Yu b,
Yu-Min Kuo c, Fong-SenWu a, Jih-Ing Chuang a,⁎
a Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
b Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
c Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Exercise induces oxidative stress, which may activate adaptive antioxidant responses. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the defense of oxidative stress by regulating the expression of antioxidant enzymes, gamma-glutamylcysteine ligase (γGCL) and heme oxygenase-1 (HO-1). We investigated whether treadmill exercise protects dopaminergic neurons by regulating the Nrf2 antioxidant system in a 1-methyl-4-phenylpyridine (MPP⁺)-induced parkinsonian rat model. We found that MPP⁺ induced early decreases in total glutathione level and Nrf2/γGCLC (catalytic subunit of γGCL) expression, but late upregulation of HO-1 expression in association with loss of nigral dopaminergic neurons and downregulation of tyrosine hydroxylase and dopamine transporter expression in the striatum. Treadmill exercise for 4 weeks induced upregulation of Nrf2 and γGCLC expression, and also prevented the MPP⁺-induced downregulation of Nrf2/γGCLC/glutathione, HO-1 upregulation, and nigrostriatal dopaminergic neurodegeneration. Moreover, the protective effect of exercise was blocked by the knockdown of Nrf2 using a lentivirus-carried shNrf2 delivery system. These results demonstrate an essential role of Nrf2 in the exercise-mediated protective effect that exercise enhances the nigrostriatal Nrf2 antioxidant defense capacity to protect dopaminergic neurons against the MPP⁺-induced toxicity

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