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帕金森病中脑桥被盖部胆碱能神经元中线粒体 DNA 的改变。

Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinson disease.

机构信息

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom.

出版信息

Ann Neurol. 2017 Dec;82(6):1016-1021. doi: 10.1002/ana.25099. Epub 2017 Dec 4.

DOI:10.1002/ana.25099
PMID:29149768
Abstract

In Parkinson disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co-occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from postmortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation. The current results differ from studies reporting mtDNA depletion in nigral dopaminergic neurons of PD patients. Ann Neurol 2017;82:1016-1021.

摘要

在帕金森病(PD)中,线粒体功能障碍与黑质多巴胺能神经元丧失有关。胆碱能神经元丧失也同时发生,特别是在脑干结构——脑桥被盖核(PPN)内。我们从老年对照组和 PD 患者的尸检 PPN 中分离出单个胆碱能神经元。与对照组相比,PD 患者的线粒体 DNA(mtDNA)拷贝数和 mtDNA 缺失显著增加。此外,与对照组相比,PD 患者的 PPN 胆碱能神经元中含有 mtDNA 缺失水平超过 60%的神经元明显更多,这种水平与对氧化磷酸化产生有害影响相关。目前的结果与报告 PD 患者黑质多巴胺能神经元 mtDNA 耗竭的研究不同。神经病学年鉴 2017;82:1016-1021。

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