当前位置: X-MOL 学术Neurobiol. Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Distinct anti-dyskinetic effects of amantadine and group II metabotropic glutamate receptor agonist LY354740 in a rodent model: An electrophysiological perspective.
Neurobiology of Disease ( IF 5.1 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.nbd.2020.104807
Cong Zheng 1 , Yan Xu 1 , Guiqin Chen 2 , Yang Tan 1 , Weiqi Zeng 1 , Ji Wang 1 , Chi Cheng 1 , Xiaoman Yang 1 , Shuke Nie 2 , Zhentao Zhang 2 , Xuebing Cao 1
Affiliation  

L-DOPA-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy in Parkinson's disease. Characteristic neural oscillation and abnormal activity of striatal projection neurons (SPNs) are typical pathological events of LID, which would be reliable biomarkers for assessment of novel anti-dyskinetic approach if fully profiled. Glutamate dysregulation plays a critical role in the development of LID, and the group II metabotropic glutamate receptors (mGluR2/3) is believed to regulate the release of glutamate on the presynaptic terminals and inhibits postsynaptic excitation. However, the anti-dyskinetic effect of modulating mGluR2/3 is still unclear. In this study, rats with unilateral dopaminergic lesion were injected with L-DOPA (12 mg/kg, i.p.) for seven days, while motor behavior was correlated with in vivo electrophysiology analyzing LFP and single-cell activity in both primary motor cortex and dorsolateral striatum. Our study showed that as LID established, high γ oscillation (hγ) predominated during LID, the number of unstable responses of SPN to dopamine increased, and the coherence between these patterns of oscillation and spiking activity also increased. We found that pretreatment of NMDA receptor antagonist, amantadine 60 mg/kg, i.p. (AMAN) significantly reduced abnormal involuntary movements (AIMs), in parallel with the reduction of hγ oscillation, and more markedly with a decrease in unstable responses of SPNs. In contrast, a mGluR2/3 agonist, LY354740 12 mg/kg, i.p. (LY) significantly shortened the duration of LID but merely exhibited a weak effect in diminishing the intensity of LID or reversing SPN responses. Together results indicate that AIMs in the rat model of PD are associated with abnormal corticostriatal signaling, which could be reversed by NMDAR antagonism more efficiently than mGluR2/3 agonism.

中文翻译:

金刚烷胺和II组代谢型谷氨酸受体激动剂LY354740在啮齿动物模型中的明显抗运动异常作用:电生理学观点。

L-DOPA引起的运动障碍(LID)是帕金森氏病中长期多巴胺替代疗法的主要并发症。纹状体投射神经元(SPN)的特征性神经振荡和异常活动是LID的典型病理事件,如果进行全面分析,将是评估新型抗运动障碍方法的可靠生物标记。谷氨酸失调在LID的发展中起关键作用,并且据信II族代谢型谷氨酸受体(mGluR2 / 3)调节谷氨酸在突触前末端的释放并抑制突触后兴奋。但是,尚不清楚调节mGluR2 / 3的抗运动障碍作用。在这项研究中,对单侧多巴胺能性病变的大鼠注射了L-DOPA(12 mg / kg,ip),持续7天,而运动行为与体内电生理分析在原发性运动皮层和背外侧纹状体中的LFP和单细胞活性相关。我们的研究表明,随着LID的建立,在LID期间高γ振荡(hγ)占主导地位,SPN对多巴胺的不稳定反应数量增加,并且这些振荡模式和尖峰活动之间的相干性也增加。我们发现,NMDA受体拮抗剂金刚烷胺60 mg / kg ip(AMAN)的预处理可显着减少异常非自愿运动(AIM),同时减少hγ振荡,并更明显地减少SPN的不稳定反应。相反,mGluR2 / 3激动剂LY354740 12 mg / kg,ip (LY)显着缩短了LID的持续时间,但在降低LID强度或逆转SPN响应方面仅表现出微弱的作用。在一起的结果表明,PD大鼠模型中的AIM与异常的皮层皮质信号通路相关,与mGluR2 / 3激动相比,NMDAR拮抗作用可以更有效地逆转这种信号。
更新日期:2020-02-21
down
wechat
bug