Eltoprazine prevents levodopa-induced dyskinesias by reducing causal interactions for theta oscillations in the dorsolateral striatum and substantia nigra pars reticulate
Eltoprazine prevents levodopa-induced dyskinesias by reducing causal interactions for theta oscillations in the dorsolateral striatum and substantia nigra pars reticulate
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艾托拉嗪通过减少背外侧纹状体和黑质网状部 θ 振荡的因果相互作用来预防左旋多巴引起的运动障碍
DOI：
10.1016/j.neuropharm.2018.12.027
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发表时间：
2019
影响因子：
4.7
通讯作者：
Zhang Wangming
中科院分区：
文献类型：
--
作者：
Wang Qiang;Chen Jiazhi;Li Min;Lv Siyuan;Xie Zhengyuan;Li Nanxiang;Wang Ning;Wang Jinyan;Luo Fei;Zhang Wangming
左旋多巴诱导的运动障碍（LID）（帕金森病（PD）患者中发生的一种情况）中基底神经节（BG）回路内的振荡活动尚未得到充分了解。本研究的目的是首先研究主要BG输入和输出结构（分别为背外侧纹状体（dStr）和黑质网状部（SNr））中的振荡，包括振荡信息流的方向，其次研究5-HT 1A/B受体激动剂与依托哌嗪对振荡活动和异常不自主运动（AIM）特征的影响。为此，我们在AIM评分的同时对LID大鼠的dStr和SNr进行了局部场电位（LFP）电生理学检查。对LFP数据进行功率谱密度、相干性和部分格兰杰因果关系分析。相对于同时振荡活性，分析了AIM数据（含和不含依托哌嗪）。我们得到了四个主要发现。1)LID大鼠的dStr和SNr的θ波（5-8 Hz）振荡增强。2)Theta功率与最后一次LID诱导L-DOPA注射后180分钟内的AIM评分相关，但与LID发展期间的每日AIM评分总和无关。3)振荡信息从dStr流向SNr。4)相对于未给予eltoprazine的LID大鼠，长期eltoprazine降低了LID大鼠的BG θ活性，并使信息流方向性正常化。这些结果表明，dStr活性在θ振荡的因果相互作用中起着决定性作用，并且多巴胺能抑制可以通过降低dStr-SNr θ活性和恢复θ网络信息流来抑制运动障碍。
Oscillatory activities within basal ganglia (BG) circuitry in L-DOPA induced dyskinesia (LID), a condition that occurs in patients with Parkinson disease (PD), are not well understood. The aims of this study were firstly to investigate oscillations in main BG input and output structures—the dorsolateral striatum (dStr) and substantia nigra pars reticulata (SNr), respectively— including the direction of oscillation information flow, and secondly to investigate the effects of 5-HT1A/B receptor agonism with eltoprazine on oscillatory activities and abnormal involuntary movements (AIMs) characteristic. To this end, we conducted local field potential (LFP) electrophysiology in the dStr and SNr of LID rats simultaneous with AIM scoring. The LFP data were submitted to power spectral density, coherence, and partial Granger causality analyses. AIM data were analyzed relative to simultaneous oscillatory activities, with and without eltoprazine. We obtained four major findings. 1) Theta band (5–8 Hz) oscillations were enhanced in the dStr and SNr of LID rats. 2) Theta power correlated with AIM scores in the 180-min period after the last LID-inducing L-DOPA injection, but not with daily summed AIM scores during LID development. 3) Oscillatory information flowed from the dStr to the SNr. 4) Chronic eltoprazine reduced BG theta activity in LID rats and normalized information flow directionality, relative to that in LID rats not given eltoprazine. These results indicate that dStr activity plays a determinative role in the causal interactions of theta oscillations and that serotonergic inhibition may suppress dyskinesia by reducing dStr-SNr theta activity and restoring theta network information flow.