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.
Abstract
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 signal-regulated 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.
维普
万方数据