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多巴胺D2型受体可能参与运动对帕金森病小鼠皮层-纹状体突触传递及自主活动的调节

赵刚, 张丹昱, 刘晓莉^*, 乔德才

北京师范大学体育与运动学院，北京 100875

摘要

本研究旨在揭示皮层-纹状体突触后膜多巴胺D2型受体(D2 receptor, D2R)在运动改善帕金森病(Parkinson’s disease, PD)小鼠行为功能障碍中的作用。选取C57/BL6雄性成年小鼠，随机分为对照组、PD组和PD运动组。纹状体两点注射6-羟多巴胺(6-hydroxydopamine, 6-OHDA)建立单侧损伤PD模型。运动干预方案为匀速跑台训练(16 m/min，40 min/d，每周5 d，共持续4周)。采用旷场实验评价小鼠自主活动能力，用离体脑片记录兴奋性突触后场电位(field excitatory postsynaptic potential, fEPSP)来评价皮层-纹状体突触传递效能，并观察D2R激动剂干预对小鼠自主活动能力和皮层-纹状体突触传递的影响。结果显示，和PD组相比，PD运动组小鼠自主运动距离和快速移动占比显著增加(P < 0.05)，递增刺激强度(0.75~3.00 pA)下fEPSP最大幅值显著降低(P < 0.05)，刺激-反应曲线斜率降低。和未给予D2R激动剂的PD小鼠相比，D2R激动剂处理的PD小鼠运动距离及快速移动占比显著增加(P < 0.05)，fEPSP峰值(P < 0.05)和刺激-反应曲线斜率降低。以上结果表明，早期运动干预或D2R激动剂干预均可抑制PD小鼠皮层-纹状体突触传递效能异常增高的现象，并改善小鼠自主运动能力，提示皮层-纹状体突触后膜D2R可能是运动改善PD小鼠自主活动能力的重要细胞分子作用靶点。

关键词： 帕金森病; 运动干预; 皮层-纹状体通路; 多巴胺II型受体; 自主活动能力; 突触传递

分类号：G807

Dopamine D2 receptor may be involved in the regulation of cortical-striatum synaptic transmission and autonomic activity in PD mice by exercise

ZHAO Gang, ZHANG Dan-Yu, LIU Xiao-Li^*, QIAO De-Cai

Physical Education and Sports College, Beijing Normal University, Beijing 100875, China

Abstract

The aim of the present study was to reveal the role of cortical-striatum postsynaptic dopamine D2 receptor (D2R) in improving motor behavioral dysfunction in Parkinson’s disease (PD) mice by exercise. C57/BL6 male adult mice were randomly divided into control, PD and PD plus exercise groups. The mice were injected with 6-OHDA in striatum to establish a unilateral injury PD model. The exercise intervention program was uniform speed running (16 m/min, 40 min/d, 5 d per week for 4 weeks). Autonomic activity of mice was tested by open field test. Cortical-striatum synaptic transmission efficiency was assessed by peak amplitude of field excitatory postsynaptic potential (fEPSP) recorded from in vitro brain slides. Meanwhile, the effects of D2R agonist on autonomic activity and cortical-striatal synaptic transmission were observed. The results showed that, co mpared with PD group, PD plus exercise group exhibited significantly increased autonomic motor distance and proportion of fast-moving (P < 0.05), as well as decreased maximum amplitude of fEPSP under increasing stimulation intensity (0.75–3.00 pA) (P < 0.05) and slope of stimulus-response curve. Compared with PD mice without D2R agonist, the movement distance and rapid movement ratio of PD mice treated with D2R agonist were increased significantly (P < 0.05), whereas fEPSP peak amplitude (P < 0.05) and the slope of stimulus-response curve were decreased. These results indicate that either early exercise intervention or D2R agonist treatment can inhibit the abnormal increase of cortical-striatum synaptic transmission and improve the autonomic motor ability in PD mice, suggesting that the cortical-striatum synaptic D2R may be an important molecular target for exercise to improve the autonomic motor ability of PD mice.

Key words: Parkinson’s disease; exercise; cortical-striatum; dopamine D2 receptor; autonomic motor ability; synaptic transmission

收稿日期：2018-11-19　　录用日期：2019-03-13

通讯作者：刘晓莉　　E-mail: xiaolil@bnu.edu.cn

DOI: 10.13294/j.aps.2019.0029

引用本文：

赵刚, 张丹昱, 刘晓莉, 乔德才. 多巴胺D2型受体可能参与运动对帕金森病小鼠皮层-纹状体突触传递及自主活动的调节[J]. 生理学报 2019; 71 (4): 547-554.

ZHAO Gang, ZHANG Dan-Yu, LIU Xiao-Li, QIAO De-Cai. Dopamine D2 receptor may be involved in the regulation of cortical-striatum synaptic transmission and autonomic activity in PD mice by exercise. Acta Physiol Sin 2019; 71 (4): 547-554 (in Chinese with English abstract).