Aging is a major risk factor for the development of neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases are characterized by abnormal and prominent protein aggregation in the brain, partially due to deficiency in protein clearance. It has been proposed that alterations in microglia phagocytosis and debris clearance hasten the onset of neurodegeneration. Dystrophic microglia are abundant in aged humans, and it has been associated with the onset of disease. Furthermore, alterations in microglia containing ferritin are associated with neurodegenerative conditions. To further understand the process of microglia dysfunction during the aging process, we used hippocampal sections from Tupaia belangeri (tree shrews). Adult (mean age 3.8 years), old (mean age 6 years), and aged (mean age 7.5 years) tree shrews were used for histochemical and immunostaining techniques to determine ferritin and Iba1 positive microglia, iron tissue content, tau hyperphosphorylation and oxidized‐RNA in dentate gyrus, subiculum, and CA1‐CA3 hippocampal regions. Our results indicated that aged tree shrews presented an increased number of activated microglia containing ferritin, but microglia labeled with Iba1 with a dystrophic phenotype was more abundant in aged individuals. With aging, oxidative damage to RNA (8OHG) increased significantly in all hippocampal regions, while tau hyperphosphorylation (AT100) was enhanced in DG, CA3, and SUB in aged animals. Phagocytic inclusions of 8OHG‐ and AT100‐damaged cells were observed in activated M2 microglia in old and aged animals. These data indicate that aged tree shrew may be a suitable model for translational research to study brain and microglia alterations during the aging process.

中文翻译：

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老年 Tupaia belangeri 海马中氧化应激增加、tau 过度磷酸化和营养不良的小胶质细胞。

衰老是神经退行性疾病发展的主要风险因素。阿尔茨海默病和其他神经退行性疾病的特征是大脑中异常和显着的蛋白质聚集，部分原因是蛋白质清除不足。有人提出，小胶质细胞吞噬作用和碎片清除的改变会加速神经变性的发生。营养不良的小胶质细胞在老年人中很丰富，它与疾病的发生有关。此外，含有铁蛋白的小胶质细胞的改变与神经退行性疾病有关。为了进一步了解衰老过程中小胶质细胞功能障碍的过程，我们使用了来自Tupaia belangeri 的海马切片（树鼩）。成年树鼩（平均年龄 3.8 岁）、老年（平均年龄 6 岁）和老年（平均年龄 7.5 岁）树鼩被用于组织化学和免疫染色技术，以确定铁蛋白和 Iba1 阳性小胶质细胞、铁组织含量、tau 过度磷酸化和氧化-齿状回、下突和 CA1-CA3 海马区的 RNA。我们的结果表明，年老的树鼩呈现出更多数量的含有铁蛋白的活化小胶质细胞，但用 Iba1 标记的具有营养不良表型的小胶质细胞在老年个体中更为丰富。随着衰老，所有海马区域的 RNA (8OHG) 氧化损伤显着增加，而老年动物的 DG、CA3 和 SUB 中的 tau 过度磷酸化 (AT100) 增强。在老年和老年动物的活化 M2 小胶质细胞中观察到 8OHG 和 AT100 损伤细胞的吞噬包涵体。这些数据表明，老年树鼩可能是研究衰老过程中大脑和小胶质细胞改变的转化研究的合适模型。