Histamine Modulation of the Basal Ganglia Circuitry in the Motor Symptoms of Parkinson's Disease

IF 5 1区医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2025-02-27 DOI:10.1111/cns.70308

Hui-Xian Zhu, Wei-Wei Lou, Yi-Miao Jiang, Alina Ciobanu, Chen-Xin Fang, Cheng-Ye Liu, Yan-Li Yang, Jing-Yang Cao, Ling Shan, Qian-Xing Zhuang

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Abstract

Purpose of Review

Parkinson's disease (PD) is characterized by dopaminergic system dysfunction that results from the degeneration of neurons in the substantia nigra. However, studies suggest that other neurotransmitters, especially histamine, may also play a role in the development of PD.

Recent Findings

Numerous studies show that histamine levels in the basal ganglia significantly change in PD pathology, correlating with motor symptoms observed in animal models of PD. Histamine activates H1R or H4R on microglia in the substantia nigra, triggering an inflammatory response and promoting dopaminergic neuron degeneration. Additionally, histamine modulates neuronal excitability and firing activity (firing rate and pattern) by activating H1R, H2R, or H3R on neurons in the basal ganglia nucleus, ultimately impacting normal motor behavior as well as motor symptoms in models of PD.

Summary

This review presents the role of histamine and its receptor ligands in the basal ganglia nuclei, along with downstream ion channels linked to histamine receptors that influence immune response, neuronal excitability, and firing activity in PD. It highlights their effects on neuronal firing and their connection to PD motor symptoms. Investigating new ligands targeting basal ganglia histamine receptors and associated ion channels may facilitate the development of novel treatments for PD.

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帕金森病运动症状中基底神经节回路的组胺调节

帕金森病（PD）以黑质神经元变性导致的多巴胺能系统功能障碍为特征。然而，研究表明，其他神经递质，特别是组胺，也可能在PD的发展中发挥作用。大量研究表明，基底神经节组胺水平在PD病理过程中发生显著变化，与PD动物模型中观察到的运动症状相关。组胺激活黑质小胶质细胞上的H1R或H4R，引发炎症反应，促进多巴胺能神经元变性。此外，组胺通过激活基底神经节核神经元上的H1R、H2R或H3R来调节神经元的兴奋性和放电活动（放电速率和模式），最终影响PD模型的正常运动行为和运动症状。本文综述了组胺及其受体配体在基底神经节核中的作用，以及与组胺受体相连的下游离子通道，这些离子通道影响PD患者的免疫反应、神经元兴奋性和放电活性。它强调了它们对神经元放电的影响以及它们与PD运动症状的联系。研究基底节区组胺受体和相关离子通道的新配体可能促进PD新治疗方法的发展。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.