纹状体D2-MSNs可塑性介导运动改善帕金森病运动功能障碍的研究进展

Research progress on striatal D2-MSNs plasticity mediated improvement of motor dysfunction by exercises in Parkinson’s disease

帕金森病(Parkinson’s disease,PD)是常见的神经退行性疾病,其重要的病理学基础为黑质多巴胺(dopamine,DA)能神经元丢失与纹状体DA减少。在基底神经节环路内,DA通过不同亚型的纹状体中等多棘神经元调节运动行为。越来越多的研究显示,DA受体2型中等多棘神经元(D2-dopamine receptor expressing medium spiny neurons,D2-MSNs)可塑性的改变对调节PD运动功能障碍至关重要。有氧运动可通过调节DA受体活性及其下游的细胞外信号调节激酶(extracellular signal-regulated kinase,Erk)信号通路参与D2-MSNs结构与功能的重塑过程,预防或改善PD相关运动功能障碍。本文综述了PD发病后纹状体D2-MSNs结构和功能可塑性的关键调控机制,并重点讨论了纹状体D2-MSNs在有氧运动改善PD运动功能障碍中的作用。

Parkinson’s disease(PD),a prevalent neurodegenerative condition,manifests predominantly through the degeneration of nigrostriatal dopaminergic(DA)pathways,culminating in a notable depletion of striatal dopamine.This pathophysiological process critically impairs the DA-mediated regulation of motor behaviors within the basal ganglia circuitry,particularly impacting various subtypes of striatal medium spiny neurons.Recent advancements in neuroscientific research have illuminated the pivotal role of D2-dopamine receptor expressing medium spiny neurons(D2-MSNs)plasticity in coordinating motor control in PD.Intriguingly,aerobic exercise emerges as a potent therapeutic intervention,capable of preventing or improving motor impairments.This ameliorative effect is mediated through the modulation of DA receptor activity and the consequent activation of downstream extracellular signalregulated kinase(Erk)signaling pathway.This article meticulously reviewed the intricate regulatory mechanisms governing the structural and functional plasticity of striatal D2-MSNs in the context of PD.It particularly emphasized the transformative impact of aerobic exercise on motor deficits in PD,attributing this effect to the modulation of striatal D2-MSNs.