PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine\'s amelioration of dyskinesia at the electrophysiological level in rats.
Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity.
We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia.
Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.
Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity.
We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia.
Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.
摘要：
目的：帕金森病（PD）是一种广泛性神经退行性疾病，左旋多巴(L-dopa)是其优选的治疗方法。左旋多巴诱导的运动障碍（LID）的病理生理机制，长期服用左旋多巴最常见的并发症，仍然晦涩难懂。积累的证据表明，多巴胺能系统以及非多巴胺能系统有助于LID的发展。作为5-羟色胺1A/1B受体激动剂，依托拉嗪改善运动障碍，尽管对其电生理机制知之甚少。本研究的目的是探讨慢性左旋多巴给药的累积效应以及埃洛拉嗪在电生理水平上改善大鼠运动障碍的潜在机制。
方法：对不同病理状态下初级运动皮层（M1）和背外侧纹状体（DLS）的局部场电位（LFP）数据进行神经电生理分析技术，以获取功率谱密度信息。θ-γ相位-振幅耦合(PAC),和功能连接。进行行为测试和AIMs评分以验证PD模型的建立并评估LID严重程度。
结果：我们在运动障碍状态下检测到夸大的伽马活动，在不同的地区具有不同的特征和影响。M1中的伽马振荡是窄带的，而在DLS中有宽带外观。LID状态下纹状体夸张的theta-gammaPAC有助于宽带伽马振荡，在M1中，非周期性校正的皮层β功率与非周期性校正的γ功率密切相关。左旋多巴给药后，γ波段的M1-DLS相干性和锁相值（PLV）得到增强。埃托拉齐干预减少了伽马振荡，DLS中的theta-gammaPAC,和相干和PLVs在γ波段缓解运动障碍。
结论：过度的皮质γ振荡是运动障碍的一个令人信服的临床指标。增强PAC的检测和伽马带振荡的功能连通性可用于指导和优化深部脑刺激参数。埃托拉嗪治疗运动障碍具有潜在的临床应用价值。
方法：对不同病理状态下初级运动皮层（M1）和背外侧纹状体（DLS）的局部场电位（LFP）数据进行神经电生理分析技术，以获取功率谱密度信息。θ-γ相位-振幅耦合(PAC),和功能连接。进行行为测试和AIMs评分以验证PD模型的建立并评估LID严重程度。
结果：我们在运动障碍状态下检测到夸大的伽马活动，在不同的地区具有不同的特征和影响。M1中的伽马振荡是窄带的，而在DLS中有宽带外观。LID状态下纹状体夸张的theta-gammaPAC有助于宽带伽马振荡，在M1中，非周期性校正的皮层β功率与非周期性校正的γ功率密切相关。左旋多巴给药后，γ波段的M1-DLS相干性和锁相值（PLV）得到增强。埃托拉齐干预减少了伽马振荡，DLS中的theta-gammaPAC,和相干和PLVs在γ波段缓解运动障碍。
结论：过度的皮质γ振荡是运动障碍的一个令人信服的临床指标。增强PAC的检测和伽马带振荡的功能连通性可用于指导和优化深部脑刺激参数。埃托拉嗪治疗运动障碍具有潜在的临床应用价值。
