运动通过调节皮层-纹状体通路功能连接可塑性改善PD模型大鼠行为  

Treadmill Exercise Improves Motor Performance by Regulating the Plasticity of Corticostriatal Functional Connection in Hemiparkinsonian Rats

作　　者：时凯旋 刘晓莉[1] 乔德才[1] SHI Kaixuan;LIU Xiaoli;QIAO Decai(College of P.E and Sports,Beijing Normal University,Beijing 100875,China;Department of Physical Education,China University of Geosciences,Beijing 100083,China)

机构地区：[1]北京师范大学体育与运动学院,北京100875 [2]中国地质大学体育部,北京100083

出　　处：《体育科学》2020年第6期49-58,共10页China Sport Science

基　　金：国家自然科学基金(31571221)。

摘　　要：目的:帕金森病(Parikinson’s disease,PD)是起始于黑质-纹状体通路多巴胺(dopamine,DA)损耗的一种神经退行性疾病,运动皮层-纹状体通路功能连接强度改变被认为是导致PD运动障碍产生的重要病理基础。通过计算神经信号振荡同步性量化分析皮层-纹状体之间功能连接强度,并从代谢型谷氨酸受体(mGluR2/3)介导的谷氨酸(glutamte,Glu)兴奋性传导角度来阐释运动干预PD的神经调控机制。方法:清洁级SD大鼠随机分为3组:假手术组(Control)、PD组(PD)和PD运动组(PD+Ex),于右侧内侧前脑束(medial forebrain bundle,MFB)注射6-羟基多巴(6-hydroxydopamine hydrobromide,6-OHDA)建立单侧PD大鼠模型。采用阿朴吗啡(apomorphine,APO)旋转行为实验,并结合黑质和纹状体酪氨酸羟化酶(tyrosine hydroxylase,TH)表达水平评价PD大鼠模型的可靠性。PD+Ex组大鼠进行为期4周的跑台运动干预(11 m/min,30 min/天,5天/周),在第0、1、2、3、4周末检测各组大鼠自主活动行为;利用在体多通道电生理技术,观察各组大鼠运动皮层和纹状体局部场电(local field potentials,LFPs)活动;采用微透析-高效液相色谱联用技术检测纹状体胞外Glu浓度,结合生化技术检测纹状体mGluR2/3蛋白表达。结果:自主行为测试结果显示,PD+Ex组较PD组快速和慢速移动时间占比均显著增加(P<0.05),静止状态时间占比显著降低(P<0.05),且大鼠自主活动行为改善效果具有时间依赖性。电生理结果表明,PD+Ex组运动皮层-纹状体β振荡的相干系数和相位同步指数较PD组显著下降(P<0.05),且变化也具有时间依赖性。蛋白检测结果显示,PD+Ex组纹状体mGluR2/3表达较PD组显著上调(P<0.01);递质检测结果显示,PD+Ex组纹状体胞外Glu浓度较PD组显著降低(P<0.01)。结论:PD模型大鼠自主活动行为降低伴随运动皮层-纹状体通路功能连接异常。运动干预通过调节运动皮层-纹状体通路功能连接有效改善PD模型大鼠自�Objective:Parkinson’s disease(PD)is a progressive neurodegenerative disorder that is characterized by the loss of dopamine(DA)due to the degeneration of substantia nigra pars compacta dopaminergic neurons.Functional connection changes of cortical-striatum pathway is considered to be the fundamental pathological feature of motor dysfunction in PD patients.In order to explain the possible mechanism of motor improving the behavioral function of PD model rats.This study aimed to quantify the strength of functional connectivity between the motor cortex and striatum by measuring oscillation synchronization,and to investigate the mechanism underlying behavioral improvement by exercise intervention in the view of metabotropic glutamate receptors 2/3(mGluR2/3)-mediated plasticity.Methods:Thirty adult male SD rats were randomly divided into three groups:shamoperation group(Control),PD group(PD)and PD with exercise group(PD+Ex).6-hydroxydopamine(6-OHDA)was injected into medial forebrain bundle(MFB)in the right brain of SD rat to establish the parkinsonian rat model,and apomorphine(APO)-induced rotational test combined with TH-immunoreactivity in the striatum and substantia nigra pars compacta were performed to evaluate the reliability of PD model.Exercise intervention was applied to the PD+Ex group for 4 weeks(11 m/min,30 min/d,5 d/w).Locomotor behavior test were carried out at the end of 0/1/2/3/4 week;the local field potentials(LFPs)in the motorcortex and striatum of freely moving parkinsonian were recorded by using vivo multichannel recording technology;the extracellular glutamate levels and mGluR2/3 protein levels were measured by using microdialysis inserted-high performance liquid chromatography(HPLC)and biochemical tests,respectively.Results:Compared with the PD group,the PD+Ex group spent significantly more time performing fast and slow movements(P<0.05),and significantly less time in resting(P<0.05),and these improvements in locomotor behavior showed time-dependent.Electrophysiological results indicated that the

关 键 词：运动 帕金森病 功能性连接可塑性 皮层-纹状体通路 同步振荡 谷氨酸 

分 类 号：G804.7[文化科学—运动人体科学]