摘要
目的:揭示帕金森病(Parkinson’s disease,PD)模型大鼠纹状体中等多棘神经元(medium spiny neurons,MSNs)树突棘运动依赖可塑性发生的细胞靶点。方法:清洁级SD大鼠随机分为3组:假手术组(Con组)、PD组和PD运动组(PD+Ex组),采用神经毒素6-羟基多巴胺(6-Hydroxydopamine,6-OHDA)注射于大鼠右脑内侧前脑束(medial forebrain bundle,MFB)建立偏侧损毁PD模型大鼠,假手术组于相同部位给予同等剂量的生理盐水作为对照组。阿扑吗啡(apomorphine,APO)诱导旋转行为测试并结合黑质和纹状体酪氨酸羟化酶(tyrosine hydroxxylase,TH)免疫组织化学染色评价PD模型的可靠性。PD+Ex组于手术后1周开始进行跑台训练干预(11 m/min,30 min/d,5 d/w,共4周)。采用爬杆实验评价模型大鼠的四肢协调能力;采用逆行神经示踪结合荧光素标记方法区分D1-MSNs和D2-MSNs;采用免疫印迹技术检测纹状体突触连接蛋白突触后致密物-95(postsynaptic density-95,PSD-95)和突触素(synaptophysin,Syn)的表达水平。结果:APO诱导的旋转行为测试和TH免疫组织化学检测结果表明,PD大鼠模型可靠,成模率为75%。爬杆实验结果表明,与Con组相比,PD组大鼠爬杆延迟时间显著延长(P<0.01);与PD组相比,PD+Ex组大鼠爬杆延迟时间显著缩短(P<0.05)。逆行神经示踪结合荧光素标记结果表明,与Con组相比,PD组和PD+Ex组大鼠D1-MSNs树突棘密度无显著改变(P>0.05);PD组大鼠D2-MSNs树突棘密度显著降低(P<0.01);与PD组相比,PD+Ex组大鼠D2-MSNs树突棘密度显著增加(P<0.05)。免疫印迹结果表明,与Con组相比,PD组大鼠纹状体PSD-95、Syn表达水平显著下调(P<0.01);与PD组相比,PD+Ex组大鼠纹状体PSD-95、Syn表达水平显著上调(P<0.05)。结论:PD模型大鼠纹状体D2-MSNs树突棘丢失,跑台运动干预可选择性降低PD模型大鼠纹状体D2-MSNs树突棘丢失。运动通过上调突触连接蛋白表达促进PD模型大鼠纹状体MSNs形态结构重塑。纹状体MSNs树�
Objective:To reveal the target cells of striatum MSNs plasticity depending on exercise in PD model rats.Methods:Heanth adult SD rats were randomly divided into three groups:sham operation group(Con),PD group(PD)and PD with exercise group(PD+Ex).6-Hydroxydopamine(6-OHDA)was injected into the medial forebrain bundle(MFB)of the right brain to induce PD model of unilateral injury in rats.The sham-operation group was received the same dose of saline as the control group.The reliability of the model was evaluated by apomorphine(APO)-induced rotational behavior test combined with immunohistochemical staining of the substantial nigra and tyrosine 3-monooxygenase striatum.In the exercise group,treadmill training(11 m/min,30 min/day,5days/week,4weeks)was performed at 1 week after operation.Free locomotor activity was evaluated by open field test,D1-MNs and D2-MSNs of striatum were labeled by retrograde neural tracing and fluorescein labeling the expression of streptolysin(Syn)and streptolysin(PSD-95)in striatum were detected by Western Blotting.Results:The results of APO-induced rotation behavior test and TH immunohistochemical test showed that PD model rats were reliable and the molding rate was 75%.In the pole test,the delay time of climbing from pole top to bottom was longer in PD group compared with control group(P<0.01);compared with PD group,the delay time of climbing from pole top to bottom was decreased significantly in PD+Ex group(P<0.05).The results of retrograde nerve tracing combined with fluorescein labeling showed that the density of dendritic spines in D1-MSNs was not changed obviously in PD and PD+Ex group than that of control group,but the density of dendritic spines in D2-MSNs of PD group was decreased compared with control group(P<0.01);in addition,the density of dendritic spines in D2-MSNs of PD+Ex group was increased compared with PD group(P<0.05).Western Blotting results showed that the expression level of PSD-95 and Syn protein in striatum of PD group were decreased compared with control group(P<0.01
作者
陈平
刘晓莉
马婧
乔德才
CHEN Ping;LIU Xiaoli;MA Jing;QIAO Decai(College of P.E and Sports,Beijing Normal University,Beijing 100875,China;College of P.E Science,Jishou University,Jishou 416000,China;China Institute of Sport Science,Beijing 100061,China)
出处
《体育科学》
CSSCI
北大核心
2020年第12期54-62,共9页
China Sport Science
基金
国家自然科学基金(31571221)。
