Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra
Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra
复制标题
Marinesco 小体和细胞核平行增大，p62 逐渐沉积在黑质色素神经元中
DOI：
10.1111/neup.12647
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发表时间：
2020
期刊：
影响因子：
2.3
通讯作者：
R. Amano S. Toru M. Yamane M. Kitagawa K. Hirokawa and T. Uchihara
中科院分区：
文献类型：
--
作者：
小宮山涼一;藤井康正;R. Amano S. Toru M. Yamane M. Kitagawa K. Hirokawa and T. Uchihara
Marinesco小体（MB）是在黑质色素神经元中发现的球形核包涵体。虽然MB在衰老的大脑中很丰富，但它们与衰老过程的关系仍不清楚。在这里，我们进行了中脑色素神经元的形态计量学分析，以确定可能的影响MBs核大小。在MB的存在下，细胞核的横切面积（核面积）较大，并且与所有测试大脑中的MB面积（MB面积）相关。即使从核面积中减去MB面积后，MB相关的核增大也是显著的。此外，在扩大的MB相关核的核质中检测到p62的较高MB免疫反应性。这项对人脑的研究是第一个定量方法，证明了MB相关的核扩大和小核质物质的进行性积累。虽然细胞肥大通常被认为是细胞功能上调的指示，但情况可能并非总是如此。这些研究结果表明，年龄相关的泛素-蛋白酶体和自噬系统活性下降以及不可降解物质的停滞是解释黑质神经活动年龄相关性下降的候选机制之一。
Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB‐associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB‐associated nuclei. This study on human brains is the first quantitative approach demonstrating MB‐associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age‐related decline of ubiquitin‐proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age‐related decline of neural activity in the substantia nigra.