Exercise protects against MPTP-induced neurotoxicity in mice.
Exercise protects against MPTP-induced neurotoxicity in mice.
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DOI：
10.1016/j.brainres.2010.01.053
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发表时间：
2010-06-23
期刊：
影响因子：
2.9
通讯作者：
Smeyne, Richard J.
中科院分区：
文献类型：
--
作者：
Gerecke, Kimberly M.;Jiao, Yun;Pani, Amar;Pagala, Vishwajeeth;Smeyne, Richard J.
运动已被证明在多种神经退行性模型中具有有效的神经保护作用，包括帕金森病 (PD) 的 1-甲基-4 苯基-1,2,3,6-四氢吡啶 (MPTP) 模型。为了确定 DA 神经保护所需的关键运动持续时间，在用盐水或 MPTP 治疗之前让小鼠跑步 1、2 或 3 个月。 SNpc 中 DA 神经元的定量显示，与盐水处理的小鼠相比，允许不受限制地奔跑 1 或 2 个月的小鼠在 MPTP 给药后损失了大量神经元；然而，3 个月的锻炼可以完全防止 MPTP 引起的神经毒性。为了确定 DA 神经保护的临界运动强度，在用盐水或 MPTP 治疗之前 3 个月，将小鼠的跑步限制为完全跑步组的 1/3 或 2/3。 SNpc 中 DA 神经元的定量显示，跑步受到限制的小鼠由于 MPTP 毒性而损失了大量 DA 神经元；然而，2/3 跑步组表现出部分保护。对 DA 及其代谢物 DOPAC 和 HVA 的神经化学分析表明，运动还能在功能上保护神经元免受 MPTP 诱导的神经毒性。 SN 和 STR 组织的蛋白质组学分析表明，3 个月的运动会诱导与能量调节、细胞代谢、细胞骨架和细胞内信号事件相关的蛋白质发生变化。总而言之，这些数据表明运动可以有效保护 DA 神经元免受急性 MPTP 毒性的影响，这表明这种简单的生活方式元素也可能对人类预防 PD 产生显着的保护作用。
Exercise has been shown to be potently neuroprotective in several neurodegenerative models, including 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) model of Parkinson’s disease (PD). In order to determine the critical duration of exercise necessary for DA neuroprotection, mice were allowed to run for either 1, 2 or 3 months prior to treatment with saline or MPTP. Quantification of DA neurons in the SNpc show that mice allowed to run unrestricted for 1 or 2 months lost significant numbers of neurons following MPTP administration as compared to saline treated mice; however, 3 months of exercise provided complete protection against MPTP-induced neurotoxicity. To determine the critical intensity of exercise for DA neuroprotection, mice were restricted in their running to either 1/3 or 2/3 that of the full running group for 3 months prior to treatment with saline or MPTP. Quantification of DA neurons in the SNpc show that mice whose running was restricted lost significant numbers of DA neurons due to MPTP toxicity; however, the 2/3 running group demonstrated partial protection. Neurochemical analyses of DA and its metabolites DOPAC and HVA show that exercise also functionally protects neurons from MPTP induced neurotoxicity. Proteomic analysis of SN and STR tissues indicates that 3 months of exercise induces changes in proteins related to energy regulation, cellular metabolism, the cytoskeleton, and intracellular signaling events. Taken together, these data indicate that exercise potently protects DA neurons from acute MPTP toxicity, suggesting that this simple lifestyle element may also confer significant protection against developing PD in humans.
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