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Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra
Neuropathology ( IF 1.3 ) Pub Date : 2020-03-22 , DOI: 10.1111/neup.12647
Ryota Amano 1, 2 , Shuta Toru 1 , Michio Yamane 3 , Masanobu Kitagawa 4, 5 , Katsuiku Hirokawa 4 , Toshiki Uchihara 1, 2
Affiliation  

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.

中文翻译:

Marinesco 小体和细胞核的平行增大以及 p62 在黑质色素神经元中的逐渐沉积

Marinesco 小体 (MB) 是在黑质色素神经元中发现的球形核内含物。尽管 MB 在衰老的大脑中含量丰富,但它们与衰老过程的关系仍不清楚。在这里,我们对中脑色素神经元进行了形态计量分析,以确定 MB 对核大小的可能影响。在 MB 存在的情况下,细胞核的横切面积(核面积)更大,并且与所有测试大脑中的 MB 面积(MB 面积)相关。即使从核区域中减去 MB 区域,MB 相关的核增大也是显着的。此外,在扩大的 MB 相关核的核质中检测到 p62 的更高 MB 免疫反应性。这项对人脑的研究是第一个证明与 MB 相关的核扩大和小核质材料逐渐积累的定量方法。尽管细胞肥大通常被认为是细胞功能上调的迹象,但情况并非总是如此。这些发现表明,泛素-蛋白酶体和自噬系统活动与年龄相关的下降以及不可降解材料的停滞是解释黑质中神经活动与年龄相关的下降的候选机制之一。
更新日期:2020-03-22
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