Jiang Yimiao, Qi Zengxin, Zhu Huixian, Shen Kangli, Liu Ruiqi, Fang Chenxin, Lou Weiwei, Jiang Yifan, Yuan Wangrui, Cao Xin, Chen Liang, Zhuang Qianxing
Department of Physiology, School of Medicine, Nantong University, Nantong, Jiangsu Province, China.
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Neural Regen Res. 2025 Jun 1;20(6):1628-1643. doi: 10.4103/NRR.NRR-D-23-01660. Epub 2024 Jun 3.
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 tremor-dominant 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.
苍白球在基底神经节回路中起关键作用。帕金森病的特征是黑质中产生多巴胺的细胞退化，这导致大脑中多巴胺缺乏，随后表现为各种运动和非运动症状。本综述旨在总结苍白球在帕金森病运动和非运动表现中的作用。内侧苍白球中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及僵硬表现出强烈的相关性。与运动迟缓及僵硬高度相关的β振荡增加，受外侧苍白球调节。此外，运动迟缓及僵硬与皮质-基底神经节-丘脑皮质环路内多巴胺能投射的丧失密切相关。静止性震颤归因于病理信号从基底神经节通过运动皮层传递至小脑腹侧中间核回路。皮质-纹状体-苍白球环路负责介导与苍白球相关的睡眠障碍。药物治疗和深部脑刺激是针对帕金森病中苍白球的主要治疗策略。药物治疗是帕金森病早期运动症状的主要治疗方法，而深部脑刺激已在临床上被证明对缓解晚期帕金森病患者的症状有效，特别是对左旋多巴引起的运动障碍。针对内侧苍白球的深部脑刺激可改善震颤为主型和非震颤为主型帕金森病患者的运动功能，而针对外侧苍白球的深部脑刺激可改变整个基底神经节-丘脑网络神经活动的时间模式。因此，苍白球神经元的组成、作用于它们的神经递质、它们的电活动以及它们形成的神经回路，可在临床实践中指导寻找治疗帕金森病的新型多靶点药物。研究与苍白球相关的深部脑刺激潜在的核内及神经回路机制，可在尽量减少深部脑刺激引起的副作用的同时，促进对运动和非运动症状的管理。
