Department for Brain Research, Research Center of Neurology, 125367 Moscow, Russia.
Department for Histology, Embryology, and Cytology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Int J Mol Sci. 2022 Sep 14;23(18):10695. doi: 10.3390/ijms231810695.
Accumulating data suggest that the brain undergoes various changes during aging. Among them are loss of both white and gray matter, neurons and synapses degeneration, as well as oxidative, inflammatory, and biochemical changes. The above-mentioned age-related features are closely related to autophagy and mitochondria. Therefore, we aimed to reveal the most peculiar morphological features of brain nervous tissue and to characterize the expression of autophagy and mitochondrial immunohistochemical biomarkers in neurons of different human brain zones during aging. Counting the number of neurons as well as Microtubule-associated proteins 1A/1B light chain 3B (LC3B), Heat shock protein 70 (HSP70), Lysosome-associated membrane protein type 2A (LAMP2A), Alpha subunit of ATP synthase (ATP5A), and Parkinson disease protein 7 (DJ1) immunohistochemical staining were performed on FFPE samples of human prefrontal cortex, corpus striatum, and hippocampus obtained from autopsy. Statistical analysis revealed a loss of neurons in the studied elderly group in comparison to the young group. When the expression of macroautophagy (LC3B), chaperon-mediated autophagy (HSP70, LAMP2A), and mitochondrial respiratory chain complex V (ATP5A) markers for the young and elderly groups were compared, the latter was found to have a significantly higher rate of optical density, whilst there was no significance in DJ1 expression. These findings, while preliminary, suggest that both autophagy and mitochondria are involved in neuronal maintenance during aging and could indicate their potential role in adaptive mechanisms that occur in aging.
越来越多的证据表明,大脑在衰老过程中会发生各种变化。其中包括白质和灰质、神经元和突触的丧失,以及氧化、炎症和生化变化。上述与年龄相关的特征与自噬和线粒体密切相关。因此,我们旨在揭示脑组织最独特的形态特征,并描述在衰老过程中不同人脑区神经元中自噬和线粒体免疫组织化学生物标志物的表达情况。我们对来自尸检的人前额叶皮层、纹状体和海马体的 FFPE 样本进行了神经元计数以及微管相关蛋白 1A/1B 轻链 3B(LC3B)、热休克蛋白 70(HSP70)、溶酶体相关膜蛋白 2A(LAMP2A)、ATP 合酶 α 亚基(ATP5A)和帕金森病蛋白 7(DJ1)免疫组织化学染色。统计分析显示,与年轻组相比,研究中的老年组神经元数量减少。当比较年轻组和老年组巨自噬(LC3B)、伴侣介导的自噬(HSP70、LAMP2A)和线粒体呼吸链复合物 V(ATP5A)标志物的表达时,发现后者的光密度明显更高,而 DJ1 的表达则没有差异。这些发现虽然初步,但表明自噬和线粒体都参与了衰老过程中神经元的维持,并可能表明它们在衰老过程中发生的适应性机制中的潜在作用。