Electrophysiological Alterations in the Progression of Parkinson's Disease and the Therapeutic Effect of Tetrabenazine on Rats With Levodopa-Induced Dyskinesia

IF 4.8 1区 医学 Q1 NEUROSCIENCES
Yuewei Bi, Pengfei Wang, Min Li, Zhuyong Wang, Siyuan Lv, Yong Yang, Wangming Zhang
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Abstract

Aims

Dopamine replacement therapy is the backbone of Parkinson's disease (PD) treatment. However, long-term levodopa (L-DOPA) administration can lead to the severely disabling motor complication L-DOPA-induced dyskinesia (LID), for which standard, effective therapy is currently lacking. This study was conducted to characterize the distinct neural electrophysiological patterns involved in the progression of PD and to examine the efficacy of tetrabenazine, a vesicular monoamine transporter-2 inhibitor, in alleviating dyskinesia and its underlying electrophysiological mechanism.

Methods

Electrophysiological analysis was performed to obtain power spectrum density and functional connectivity information from local field potential (LFP) data recorded from the primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states in PD model rats. Behavioral tests and abnormal involuntary movements (AIMs) scoring were conducted to confirm PD model establishment and assess LID severity.

Results

Increased beta oscillations and abnormally strengthened beta causality in the M1 → DLS direction and exaggerated beta-band M1–DLS functional connectivity were observed in the PD state. L-DOPA administration suppressed beta activity and augmented gamma power in the M1 and DLS, with increased gamma causality in the M1 → DLS direction and beta causality in the DLS → M1 direction, as well as elevated gamma-band M1–DLS functional connectivity. Tetrabenazine strongly ameliorated dyskinetic manifestations. It suppressed gamma power in the M1 and DLS, reduced gamma causality and increased beta causality in the M1 → DLS direction, reduced beta causality in the DLS → M1 direction, and reduced gamma-band M1–DLS functional connectivity.

Conclusion

Tetrabenazine abrogated aberrant gamma activity to improve LID symptoms, which provides compelling evidence for its future clinical application in LID therapy.

Abstract Image

帕金森病进展中的电生理改变及Tetrabenazine对左旋多巴诱导的运动障碍大鼠的治疗作用
目的多巴胺替代疗法是帕金森病(PD)治疗的支柱。然而,长期服用左旋多巴(L-DOPA)可导致严重致残性运动并发症左旋多巴诱导的运动障碍(LID),目前缺乏标准有效的治疗方法。本研究旨在描述PD进展过程中不同的神经电生理模式,并研究特苯那嗪(一种水泡单胺转运蛋白-2抑制剂)缓解运动障碍的疗效及其潜在的电生理机制。方法对PD模型大鼠不同病理状态下初级运动皮层(M1)和背外侧纹状体(DLS)局部场电位(LFP)数据进行电生理分析,获取功率谱密度和功能连接信息。行为测试和异常不自主运动(AIMs)评分证实PD模型的建立,评估LID的严重程度。结果PD状态下M1→DLS方向β振荡增加,β因果关系异常增强,β带M1 - DLS功能连接增强。左旋多巴抑制了M1和DLS的β活性,增强了γ功率,M1→DLS方向的γ因果关系增加,DLS→M1方向的β因果关系增加,γ波段M1 - DLS功能连接增强。四苯那嗪可显著改善运动障碍的表现。它抑制了M1和DLS的gamma功率,降低了M1→DLS方向的gamma因果关系,增加了beta因果关系,降低了DLS→M1方向的beta因果关系,降低了gamma波段M1 - DLS的功能连通性。结论Tetrabenazine可消除异常γ活性,改善LID症状,为其在LID治疗中的临床应用提供了有力的证据。
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来源期刊
CNS Neuroscience & Therapeutics
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.
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