CB1受体参与运动疲劳损害小鼠皮层-纹状体通路eCB-LTD的调节

摘要

Objective: The aim of the present study is to investigate the effect of exercise-induced fatigue on corticostriatal synaptic plasticity by observing the changes of endocannabinoid-mediated long-term depression (eCB-LTD) after exercise-induced fatigue. Methods: Adult male C57BL/6 mice were randomly divided into two groups: control mice and exercise-induced fatigue (EF) mice. Electric treadmill was used to establish a repetitive exhausted EF mouse model. The corticostriatal LTD of two groups were examined by using in vitro field excitatory postsynaptic potential (fEPSP) recording technique. And the CB1 receptor antagonist AM251 was applied to examine whether this corticostriatal LTD was eCB-dependent. In vitrowhole-cell patch clamp recording was used to detect the basic electrophysiological properties of medium spiny neurons (MSNs). Western blotting was used to examine the expression of CB1 receptor in the striatum. Results: 1) The corticostriatal LTD in EF mice was significantly impaired compared with the control group (P < 0.01), and the LTD was blocked by CB1 receptor antagonist AM251, thus it was eCB-LTD. 2) The basic electrophysiological properties of MSNs in EF mice were normal (P>0.05). 3) Compared with the control group, the striatal expression of CB1 receptor in EF mice was significantly increased (P<0.01). Conclusion: The corticostriatal eCB-LTD was impaired in EF mice, but the basic electrophysiological properties of MSNs were normal, whereas the elevated CB1 receptor expression may be a compensatory response to the eCB-LTD deficit. Our results demonstrate that EF impairs the corticostriatal eCB-LTD for the first time, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.%目的:通过研究小鼠运动疲劳后皮层-纹状体通路内源性大麻素介导的长时程抑制(endocannabinoid-mediated long-term depression,eCB-LTD)的变化,揭示运动疲劳对小鼠皮层-纹状体通路突触可塑性的影响.方法:C57/BL6雄性成年小鼠,随机分为对照组(Control)和运动疲劳组(exercise-induced fatigue,EF).利用电动跑台建立重复力竭的运动疲劳小鼠模型.采用离体脑片场电位记录技术,检测小鼠皮层-纹状体通路的LTD,并通过加入大麻素1型(cannabinoid 1,CB1)受体的拮抗剂AM251,鉴定该LTD是否依赖于内源性大麻素系统(endocannabinoid system,ECS);采用离体脑片全细胞膜片钳技术,检测小鼠纹状体中型棘状神经元(medium spiny neurons,MSNs)的基本电生理特性;采用免疫印迹技术,检测小鼠纹状体脑区CB1受体的蛋白表达含量.结果:1)与对照组相比,运动疲劳组小鼠皮层-纹状体通路的LTD显著受损(P<0.01),且该LTD能够被CB1受体拮抗剂AM251阻断,证实其为eCB-LTD.2)运动疲劳组小鼠纹状体MSNs的基本电生理特性与对照组小鼠相比无差异(P>0.05).3)与对照组相比,运动疲劳组小鼠纹状体脑区CB1受体的表达含量显著上调(P<0.01).结论:小鼠运动疲劳后皮层-纹状体通路的eCB-LTD受损,但是纹状体MSNs的基本电生理特性不变,CB1受体蛋白表达含量升高可能是对eCB-LTD受损的一种代偿反应.我们的实验结果第一次证实运动疲劳损害小鼠皮层-纹状体通路的eCB-LTD,提示皮层-纹状体通路突触可塑性异常可能是运动疲劳发生或维持的机制之一.