重新思考帕金森病运动障碍的网络决定因素。

IF 2.8 4区 医学 Q2 NEUROSCIENCES
Frontiers in Synaptic Neuroscience Pub Date : 2023-06-28 eCollection Date: 2023-01-01 DOI:10.3389/fnsyn.2023.1186484
Dalton James Surmeier, Shenyu Zhai, Qiaoling Cui, DeNard V Simmons
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引用次数: 0

摘要

大约在过去的 30 年中,纹状体多巴胺(DA)耗竭是帕金森病(PD)运动症状的网络病理生理学的关键决定因素这一观点一直主导着该领域。虽然支持这一假说的基底神经节回路模型具有极大的启发价值,但这一假说本身却从未得到过直接验证。此外,过去几十年的研究清楚地表明,这一假说所依据的网络模型未能包含基底节的关键特征,包括 DA 作用于整个基底节而不仅仅是纹状体这一事实。为了强调这一点,最近使用渐进性帕金森病小鼠模型进行的研究表明,仅纹状体DA耗竭不足以诱发帕金森病,一旦纹状体外DA信号恢复,帕金森病运动障碍就会减轻。鉴于该领域的大量发现,现在是时候为帕金森病运动障碍的网络决定因素建立一个新模型了。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rethinking the network determinants of motor disability in Parkinson's disease.

Rethinking the network determinants of motor disability in Parkinson's disease.

Rethinking the network determinants of motor disability in Parkinson's disease.

For roughly the last 30 years, the notion that striatal dopamine (DA) depletion was the critical determinant of network pathophysiology underlying the motor symptoms of Parkinson's disease (PD) has dominated the field. While the basal ganglia circuit model underpinning this hypothesis has been of great heuristic value, the hypothesis itself has never been directly tested. Moreover, studies in the last couple of decades have made it clear that the network model underlying this hypothesis fails to incorporate key features of the basal ganglia, including the fact that DA acts throughout the basal ganglia, not just in the striatum. Underscoring this point, recent work using a progressive mouse model of PD has shown that striatal DA depletion alone is not sufficient to induce parkinsonism and that restoration of extra-striatal DA signaling attenuates parkinsonian motor deficits once they appear. Given the broad array of discoveries in the field, it is time for a new model of the network determinants of motor disability in PD.

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来源期刊
CiteScore
7.10
自引率
2.70%
发文量
74
审稿时长
14 weeks
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