中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (6): 1628-1643.doi: 10.4103/NRR.NRR-D-23-01660

• 综述:退行性病与再生 • 上一篇    下一篇

苍白球在帕金森病运动和非运动症状中的作用

  

  • 出版日期:2025-06-15 发布日期:2024-11-11

Role of the globus pallidus in motor and non-motor symptoms of Parkinson’s disease

Yimiao Jiang1, #, Zengxin Qi2, 3, 4, 5, #, Huixian Zhu1, #, Kangli Shen1 , Ruiqi Liu1 , Chenxin Fang1 , Weiwei Lou1 , Yifan Jiang1 , Wangrui Yuan1 , Xin Cao1 , Liang Chen2, 3, 4, 5, *, Qianxing Zhuang1, *   

  1. 1 Department of Physiology, School of Medicine, Nantong University, Nantong, Jiangsu Province, China;  2 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China;  3 National Center for Neurological Disorders, Shanghai, China;  4 Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China;  5 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, Fudan University, Shanghai, Chin
  • Online:2025-06-15 Published:2024-11-11
  • Contact: : Liang Chen, MD, hschenliang@fudan.edu.cn; Qianxing Zhuang, PhD, qxzhuang@ntu.edu.cn
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 31771143 (to QZ); Shanghai Municipal Science and Technology Major Project, ZJ Lab, and Shanghai Center for Brain Science and Brain-Inspired Technology, No. 2018SHZDZX01 (to LC); Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program” (to ZQ).

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摘要：

苍白球是基底神经节回路的重要组成部分。帕金森病的病理特征是黑质中产生多巴胺的细胞发生变性，由此导致的大脑多巴胺缺乏会引起各种症状，包括运动和非运动症状。然而，在临床和动物模型研究中，苍白球功能障碍与帕金森病症状之间的关系仍不明确。鉴于此，文章概述了苍白球在帕金森病运动和非运动症状中的作用。①内侧苍白球小清蛋白神经元的放电活动(包括放电率和模式)与帕金森病相关的运动迟缓和僵直密切相关；此外，与运动迟缓和僵直高度相关的β振荡的增加也受外侧苍白球的调节。②运动迟缓和僵直与皮质-基底节-丘脑-皮质环路中多巴胺能投射的缺失密切相关；静止性震颤是由于病理信号从基底节通过运动皮层传递到小脑-腹侧中间核回路所致；皮质-纹状体-苍白球环路负责传递苍白球相关睡眠障碍。③针对帕利迪病苍白球的治疗策略重点是药物治疗和脑深部刺激。药物治疗是帕金森病早期运动症状的主要治疗方法。脑深部刺激的临床应用表明，它能有效缓解晚期帕金森病患者的症状，尤其是左旋多巴引起的运动障碍。内侧苍白球-脑深部刺激可以改善震颤为主型和非震颤为主型帕金森病亚型患者的运动功能，外侧苍白球-脑深部刺激会改变整个基底节-丘脑网络的神经活动时间模式。④因此，在临床实践中，寻找治疗帕金森病的多靶点新药可以从苍白球神经元的组成、作用于苍白球神经元的神经递质、苍白球神经元的电活动及其形成的神经回路等方面入手。未来深入研究与苍白球相关的脑深部刺激治疗的潜在核内和神经回路机制，有助于控制运动和非运动症状，同时最大限度地减少脑深部刺激的副反应。

https://orcid.org/0000-0002-2373-5363 (Liang Chen); https://orcid.org/0000-0002-7784-4688 (Qianxing Zhuang)

关键词:

焦虑, 基底神经节, 运动迟缓, 脑深部刺激, 抑郁, 苍白球外侧, 苍白球内侧, 苍白球外侧, 苍白球内侧, 神经回路, 帕金森病

Abstract: The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson’s disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson’s disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson’s disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson’s disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson’s disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson’s disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson’s disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson’s disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Key words: anxiety, basal ganglia, bradykinesia, deep brain stimulation, depression, globus pallidus externus, globus pallidus internus, lateral globus pallidus, medial globus pallidus, neural circuit, Parkinson’s disease