Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Beijing Institute for Brain Disorders, Beijing 100069, China; Departments of Neurobiology and Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University, Beijing 100069, China.
Brain Res Bull. 2022 Aug;186:123-135. doi: 10.1016/j.brainresbull.2022.06.004. Epub 2022 Jun 10.
Recent studied have reported that impaired striatal synaptic plasticity played a crucial role in Parkinson's disease (PD). Previous studies have suggested that electroacupuncture (EA) alleviated the motor deficits in PD patients and animal models. However, the mechanisms underlying this protection need to be further elucidated. In this study, we found that EA-induced improvement of motor deficits in the 6-hydroxydopamine (6-OHDA) rat model doesn't act through dopaminergic system. EA rescued the decreased striatal long-term potentiation (LTP) in 6-OHDA rats. In addition, the declined expression of N-methyl-D-aspartic acid receptor subunit 2B (NR2B) in the striatum was remarkably up-regulated by EA. The EA-induced improvement of LTP can be eliminated by NR2B-selective inhibitor. It is indicated that EA-induced recovery of striatal LTP was correlated with the up-regulation of NR2B subunit. EA was also found to rescue the decreased dendritic arborization and the spine density in the striatum of 6-OHDA rats. Meanwhile, EA suppressed striatal glutamate content and vesicular glutamate transporter 1 which is expressed in cortico-striatal glutamatergic projections. The decrease of striatal glutamate content induced by decortication, EA treatment or a combination of both reversed the loss of striatal spine density in 6-OHDA rats. It is indicated that EA-induced reduction of cortico-striatal glutamate transmission contributes to the recovery of striatal spine density. In conclusion, the therapeutic effect of EA on the motor deficits of 6-OHDA rats was mediated by rescuing cortico-striatal glutamate transmission and striatal synaptic plasticity.
最近的研究报告表明，纹状体突触可塑性受损在帕金森病（PD）中起着至关重要的作用。先前的研究表明，电针（EA）减轻了 PD 患者和动物模型的运动缺陷。然而，这种保护作用的机制仍需进一步阐明。在这项研究中，我们发现，电针对 6-羟多巴胺（6-OHDA）大鼠模型运动缺陷的改善作用并非通过多巴胺能系统发挥作用。电针挽救了 6-OHDA 大鼠纹状体长时程增强（LTP）的下降。此外，电针显著上调了纹状体中 N-甲基-D-天冬氨酸受体亚单位 2B（NR2B）的表达。NR2B 选择性抑制剂可消除电针诱导的 LTP 改善。这表明，电针诱导的纹状体 LTP 恢复与 NR2B 亚基的上调有关。电针还发现可挽救 6-OHDA 大鼠纹状体树突分支和棘密度的降低。同时，电针抑制了纹状体谷氨酸含量和表达于皮质纹状体谷氨酸能投射中的囊泡谷氨酸转运体 1。去皮质、电针处理或两者联合处理引起的纹状体谷氨酸含量降低逆转了 6-OHDA 大鼠纹状体棘密度的丧失。这表明，电针诱导的皮质纹状体谷氨酸传递减少有助于恢复纹状体棘密度。总之，电针对 6-OHDA 大鼠运动缺陷的治疗作用是通过挽救皮质纹状体谷氨酸传递和纹状体突触可塑性来介导的。
