中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (4): 1164-1177.doi: 10.4103/NRR.NRR-D-23-01240

• 原著:退行性病与再生 • 上一篇    下一篇

多巴胺D3受体调节帕金森病异动症皮质纹状体γ振荡

  

  • 出版日期:2025-04-15 发布日期:2024-07-03

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Pengfei Wang#, Yuewei Bi#, Min Li, Jiazhi Chen, Zhuyong Wang, Huantao Wen, Ming Zhou, Minjie Luo, Wangming Zhang*   

  1. Neurosurgery Center, Department of Pediatric Neurosurgery, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • Online:2025-04-15 Published:2024-07-03
  • Contact: Wangming Zhang, MD, wzhang@vip.126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 82071254 (to WZ).

摘要:

帕金森病长期多巴胺治疗后,可出现左旋多巴诱导异动症。而γ振荡是比较公认的左旋多巴诱导异动症标志性神经电活动。目前大多数研究仅表明左旋多巴诱导异动症状态下γ振荡功率的增大,但是γ振荡的其他电生理参数与左旋多巴诱导异动症的关系及与左旋多巴诱导异动症密切相关的多巴胺D3受体对运动障碍相关振荡的影响尚不清楚。实验发现,帕金森病状态下,皮质纹状体投射β振荡增强;而左旋多巴的应用增强了γ振荡及其非周期成分,并促进γ振荡在皮质纹状体投射的双向流动。选择性多巴胺D3受体激动剂PD128907也同样能诱发左旋多巴诱导异动症及双向流动增强的γ振荡。相反,给予选择性D3受体拮抗剂PG01037可缓解异动症症状,抑制γ振荡和皮质γ振荡非周期成分,并降低初级运动皮质向背侧纹状体方向的流动。这一结果显示了多巴胺D3受体在帕金森病异动症相关神经电活动振荡的作用,并确定了其为潜在的治疗靶点。

https://orcid.org/0000-0003-4506-6321 (Wangming Zhang); https://orcid.org/0000-0003-1758-2484 (Pengfei Wang)

关键词: 帕金森病, 左旋多巴, 运动障碍, 多巴胺D3受体, γ振荡, 局部场电位, 神经调控, 非周期成分, 初级运动皮质, 背侧纹状体, 功能连接

Abstract: Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Key words: aperiodic components, dopamine D3 receptor, dorsolateral striatum, functional connectivity, gamma oscillations, levodopa-induced-dyskinesia, local field potentials, neuromodulation, Parkinson’s disease, primary motor cortex