Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice
Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice
复制标题
DOI：
10.1016/j.brainres.2016.10.029
复制
发表时间：
2017-01-15
期刊：
影响因子：
2.9
通讯作者：
Cho, Joon-Yong
中科院分区：
文献类型：
--
作者：
Jang, Yongchul;Koo, Jung-Hoon;Cho, Joon-Yong
帕金森病（Parkinson's disease，PD）是老年人常见的以多巴胺能神经元死亡为主要表现的退行性神经系统疾病之一。耐力运动（EE）已被建议赋予神经发生和减轻PD的严重程度。然而，运动介导的神经保护作用对PD的潜在分子机制仍然是未知的。鉴于在PD的不良预后和恶性进展中升高的α-突触核蛋白和神经炎症之间的相关相互作用以及EE的抗炎作用，我们假设EE将逆转PD引起的运动功能障碍和细胞死亡。为此，我们选择了PD的药理学模型（例如，慢性注射神经毒素MPTP）。将7周龄雄性小鼠随机分为3组：安静对照组（C组，n=10）、MPTP组（M组，n=10）和MPTP +耐力运动组（ME组，n=10）。我们的数据表明，EE恢复运动功能受损的MPTP在平行减少细胞死亡。引人注目的是，EE表现出α-突触核蛋白沿着减少的促炎细胞因子（即，TNF-α和IL-1 β。支持这一点的是，EE阻止了纹状体中MPTP给药引起的Toll样受体2（TLR 2）下游信号级联反应，如MyD 88、TRAF 6和TAK-1的激活。此外，EE重建酪氨酸羟化酶的水平与C组相似。综上所述，我们的数据表明EE介导的抗PD神经保护机制是由降低的α-突触核蛋白水平赋予的抗神经炎症的基础。我们的数据提供了一个重要的见解，开发一个非药物对策对PD引起的神经元变性。
Parkinson's disease (PD) is one of the main degenerative neurological disorders accompanying death of dopaminergic neurons prevalent in aged population. Endurance exercise (EE) has been suggested to confer neurogenesis and mitigate the degree of seriousness of PD. However, underlying molecular mechanisms responsible for exercise-mediated neuroprotection against PD remain largely unknown. Given the relevant interplay between elevated alpha-synuclein and neuroinflammation in a poor prognosis and vicious progression of PD and anti-inflammatory effects of EE, we hypothesized that EE would reverse motor dysfunction and cell death caused by PD. To this end, we chose a pharmacological model of PD (e.g., chronic injection of neurotoxin MPTP). Young adult male mice (7 weeks old) were randomly divided into three groups: sedentary control (C, n=10), MPTP (M, n=10), and MPTP + endurance exercise (ME, n=10). Our data showed that EE restored motor function impaired by MPTP in parallel with reduced cell death. Strikingly, EE exhibited a significant reduction in alpha-synuclein protein along with diminished pro-inflammatory cytokines (i.e., TNF-alpha and IL-1 beta. Supporting this, EE prevented activation of Toll like receptor 2 (TLR2) downstream signaling cascades such as MyD88, TRAF6 and TAK-1 incurred by in MPTP administration in the striatum. Moreover, EE reestablished tyrosine hydroxylase at levels similar to C group. Taken together, our data suggest that an EE-mediated neuroprotective mechanism against PD underlies anti-neuroinflammation conferred by reduced levels of alpha-synuclein. Our data provides an important insight into developing a non-pharmacological countermeasure against neuronal degeneration caused by PD.