Morphological Changes in Direct Pathway Striatal Neurons in a Rat Model of Tardive Dyskinesia

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-10-02 DOI:10.1002/mds.70068

Hiroki Hikichi, Haruo Nishijima, Fumiaki Mori, Iku Kinoshita, Chieko Suzuki, Koichi Wakabayashi, Masahiko Tomiyama

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引用次数: 0

Abstract

BackgroundTardive dyskinesia (TD) and drug‐induced parkinsonism (DIP) arise from prolonged dopamine antagonist use. Although D2 receptor hypersensitivity in the indirect pathway is a proposed mechanism, the role of the direct pathway remains unclear.ObjectivesTo investigate morphological changes in the direct pathway striatal neurons' axon terminals in a rat model of haloperidol‐induced TD and DIP.MethodsMale Wistar rats received haloperidol decanoate or placebo over 6 months. Behavioral tests assessed TD‐ and DIP‐like symptoms. Axon terminals forming synapses on dendrites in the internal (GPi) and external (GPe) segments of the globus pallidus were analyzed using electron and immunoelectron microscopy.ResultsHaloperidol‐treated rats exhibited both TD‐ and DIP‐like behaviors. Vesicular gamma‐aminobutyric acid (GABA) transporter (VGAT)‐positive terminals were selectively enlarged in the GPi, and substance P colocalization indicated a direct pathway origin.ConclusionsStructural alterations in direct pathway nerve terminals may contribute to TD, challenging conventional models that focus solely on the indirect pathway. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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迟发性运动障碍大鼠直接通路纹状体神经元形态学改变

迟发性运动障碍（TD）和药物性帕金森病（DIP）是由长期使用多巴胺拮抗剂引起的。虽然间接途径中的D2受体超敏反应是一种被提出的机制，但直接途径的作用尚不清楚。目的观察氟哌啶醇诱导大鼠TD和DIP模型直接通路纹状体神经元轴突末端的形态学变化。方法小型Wistar大鼠分别给予癸酸氟哌啶醇或安慰剂治疗6个月。行为测试评估了TD -和DIP -样症状。利用电子显微镜和免疫电镜对苍白球内节段和外节段树突上形成突触的轴突末梢进行了分析。结果沙哌啶醇处理大鼠表现出TD -和DIP -样行为。囊泡γ -氨基丁酸（GABA）转运蛋白（VGAT）阳性末端在GPi中选择性扩增，P物质共定位表明了直接的途径起源。直接通路神经末梢的结构改变可能导致TD，挑战了仅关注间接通路的传统模型。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.