Treadmill exercise alleviates neuronal damage by suppressing NLRP3 inflammasome and microglial activation in the MPTP mouse model of Parkinson's disease
Treadmill exercise alleviates neuronal damage by suppressing NLRP3 inflammasome and microglial activation in the MPTP mouse model of Parkinson's disease
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DOI：
10.1016/j.brainresbull.2021.06.024
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发表时间：
2021-07-08
影响因子：
3.8
通讯作者：
Xiang, Jie
中科院分区：
文献类型：
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作者：
Wang, Wei;Lv, Ziyan;Xiang, Jie
跑台运动已被公认为是治疗帕金森病（PD）的有效策略。然而，其促进PD的确切分子机制尚不清楚。近年来，NLRP 3炎性小体被认为在PD的发病机制中起着关键作用。本研究以1甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）为模型，探讨NLRP 3炎性小体是否参与了跑台运动诱导的帕金森病神经保护和抗炎作用。将8周龄雄性小鼠（C57 BL/6系）分为4组：对照组、MPTP组、MPTP + EX组和EX组。腹腔注射MPTP建立慢性PD模型。采用旷场试验和极试验评价运动功能。结果表明，跑台运动可明显减轻MPTP所致的运动功能障碍和多巴胺能神经元变性。此外，我们还发现跑台运动抑制MPTP触发的小胶质细胞活化和NLRP 3 +/Iba-1+细胞在黑质的共定位。这些作用与通过下调TLR 4/MyD 88/NF-κ B通路抑制NLRP 3炎性体有关。总之，我们的研究表明，在MPTP诱导的PD小鼠模型中，跑台运动可以通过抑制NLRP 3炎性小体和小胶质细胞活化来有效地减轻神经元损伤。
Treadmill exercise has been recognized as an effectively therapeutic strategy for Parkinson's disease (PD). However, its exact molecular mechanism of promoting PD remain unclear. Recently, the NLRP3 inflammasome is considered to play a critical role in the pathogenesis of PD. In this study, we investigated whether NLRP3 inflammasome was involved in treadmill exercise-induced neuroprotection and anti-inflammation effect in the 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. 8-week-old male mice (C57BL/6 strain) were divided into four groups: Control, MPTP, MPTP + EX and EX. MPTP was intraperitoneally injected into mice to establish chronic PD model. The open-field test and pole test were used to assess motor function. The results showed that treadmill exercise significantly alleviated motor dysfunction and dopaminergic neuron degeneration induced by MPTP. In addition, we also found that treadmill exercise suppressed MPTP-triggered microglia activation and the co-localization of NLRP3+/Iba-1+ cells in the substantia nigra. These effects were associated with suppression NLRP3 inflammasome via down-regulation of TLR4/MyD88/NF-kappa B pathway. Overall, our study demonstrated that treadmill exercise could effectively alleviates neuronal damage via inhibition of NLRP3 inflammasome and microglial activation in MPTP-induced PD mouse model.