Investigation of mitochondrial biogenesis defects in single substantia nigra neurons using post-mortem human tissues
Investigation of mitochondrial biogenesis defects in single substantia nigra neurons using post-mortem human tissues
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DOI：
10.1016/j.nbd.2019.104631
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发表时间：
2020-02-01
影响因子：
6.1
通讯作者：
Reeve, Amy K.
中科院分区：
文献类型：
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作者：
Chen, Chun;Vincent, Amy E.;Reeve, Amy K.
据报道，健康老年人和帕金森病患者的黑质神经元存在线粒体呼吸链缺陷和线粒体DNA缺失，而广泛的神经元丢失仅见于后者。本研究旨在了解线粒体缺陷与神经元存活的病理相关性。利用死后的人类中脑，在单个神经元水平上将暴露于不同类型线粒体缺陷（包括线粒体DNA点突变、单个和多个缺失）的黑质神经元与健康老年人和帕金森病患者（无论性别）的神经元进行比较。我们在所有病例中都发现了线粒体缺陷，尽管这些缺陷在有多个缺失的线粒体疾病患者中更为严重。与其他线粒体缺陷相比，在帕金森病中检测到TFAM表达显著降低。在健康的老年神经元中检测到更高的线粒体DNA拷贝数，尽管缺失水平相当于帕金森病。我们的数据支持，在具有致病性线粒体缺陷的个体中，神经元对线粒体缺陷作出反应以生存，这种适应可能涉及TFAM。
Mitochondrial respiratory chain deficiency and mitochondria] DNA deletions are reported in substantia nigra neurons from healthy aged and Parkinson's disease cases, with extensive neuronal loss only seen in the latter. This study aimed to understand the pathological relevance of mitochondrial defects for neuronal survival. Using post-mortem human midbrain, substantia nigra neurons exposed to different types of mitochondrial defects (including mitochondrial DNA point mutations, single and multiple deletions) were compared to neurons from healthy aged and Parkinson's disease cases (either sex) at a single neuronal level. We identified mitochondrial deficiencies in all cases, though these deficiencies were more severe in the mitochondrial disease patients with multiple deletions. A significant reduction in TFAM expression was detected in Parkinson's disease compared to cases with other mitochondria] defects. Higher mitochondrial DNA copy number was detected in healthy aged neurons, despite a deletion level equivalent to Parkinson's disease. Our data support that in individuals with pathogenic mitochondrial defects, neurons respond to mitochondrial defect to survive and such an adaptation may involve TFAM.