Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.
Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.
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DOI：
10.1016/j.neurobiolaging.2016.12.001
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发表时间：
2017-03
影响因子：
4.2
通讯作者：
Arnsten AFT
中科院分区：
文献类型：
--
作者：
Morozov YM;Datta D;Paspalas CD;Arnsten AFT
在猴子和人类的衰老过程中，背外侧前额叶皮层（dlPFC）介导了早期受损的高阶认知功能。在这里，我们报告了年老恒河猴dlPFC神经元树突线粒体形态的明显变化。电子显微镜和序列切片的3D重建显示，线粒体的细片段与扩大的片段混合在一起，与年龄相关的线粒体增加，“线粒体- a- string”（MOAS）表型类似于最近在阿尔茨海默病患者中报道的情况。细细的线粒体片段与内质网池和线粒体蛋白Fis1和Drp1有关，它们都能引发线粒体裂变。这些数据表明，MOAS表型可能反映了线粒体动力学的故障，由此开始了裂变，但由于后续步骤的故障，该过程是不完整的。因此，年老的恒河猴可能特别有助于探索与年龄相关的变化，这些变化使高级皮层回路如此容易退化。
Dorsolateral prefrontal cortex (dlPFC) mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dlPFC neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the “Mitochondria-On-A-String” (MOAS) phenotype, similar to those recently reported in patients with Alzheimer's Disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the MOAS phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.