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内侧苍白球中 D1R 和 D2R 神经元亚群的特征:对帕金森病发病机制的影响。

Characterization of D1R and D2R neuronal subpopulations in the globus pallidus interna: Implications for Parkinson's disease pathogenesis.

机构信息

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Departments of Basic Medical Sciences, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

出版信息

Brain Res. 2024 Dec 15;1845:149174. doi: 10.1016/j.brainres.2024.149174. Epub 2024 Aug 19.

Abstract

Parkinson's disease (PD) ranks as the second most prevalent and rapidly growing neurodegenerative disorder. As a primary output nucleus within the basal ganglia (BG), the globus pallidus interna (GPi) is a key structure in BG information processing. It is also a key target for deep brain stimulation (DBS) to alleviate motor symptoms of PD. Previous studies have identifiedPD patients exhibiting abnormal neuronal activity in the GPi. On the other hand, various types of dopamine receptor (DR)-positive neurons have been identified within the GPi. However, the electrophysiological properties of specific DR-positive neurons within the GPi and their alterations in PD have not been addressed. In the present study, we used whole-cell patch-clamp recordings to identify two neuronal subpopulations within the GPi, dopamine D1 receptor (D1R)-positive, and dopamine D2 receptor (D2R)-positive neurons, which exhibited distinct electrophysiological properties. Additionally, significant alterations of electrophysiological properties of D2R-positive neurons within the GPi were observed in 6-hydroxydopamine (6-OHDA)-lesioned mice. These data suggest that the distinct electrophysiological properties of specific DR-positive neurons and their abnormal alteration in the GPi may be associated with PD's pathogenesis.

摘要

帕金森病(PD)是第二大常见且快速增长的神经退行性疾病。作为基底神经节(BG)的主要输出核,苍白球内侧(GPi)是 BG 信息处理的关键结构。它也是深部脑刺激(DBS)缓解 PD 运动症状的关键靶点。先前的研究已经确定 PD 患者的 GPi 中存在异常神经元活动。另一方面,已经在 GPi 中鉴定出各种类型的多巴胺受体(DR)阳性神经元。然而,GPi 内特定 DR 阳性神经元的电生理特性及其在 PD 中的变化尚未得到解决。在本研究中,我们使用全细胞膜片钳记录技术鉴定了 GPi 内的两种神经元亚群,即多巴胺 D1 受体(D1R)阳性和多巴胺 D2 受体(D2R)阳性神经元,它们表现出不同的电生理特性。此外,在 6-羟多巴胺(6-OHDA)损伤的小鼠中观察到 GPi 内 D2R 阳性神经元电生理特性的显著改变。这些数据表明,特定 DR 阳性神经元的不同电生理特性及其在 GPi 中的异常改变可能与 PD 的发病机制有关。

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