The association of astrogliosis and microglial activation with aging and Alzheimer's disease pathology in the chimpanzee brain
The association of astrogliosis and microglial activation with aging and Alzheimer's disease pathology in the chimpanzee brain
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DOI：
10.1002/jnr.25167
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发表时间：
2023-01-16
影响因子：
4.2
通讯作者：
Raghanti，Mary Ann
中科院分区：
文献类型：
--
作者：
Edler，Melissa K.;Munger，Emily L.;Raghanti，Mary Ann
衰老和神经退行性疾病，如阿尔茨海默病（AD），触发称为大脑中神经胶质激活的免疫反应。最近的证据表明，AD病理学的炎症反应存在物种差异，强调需要进行额外的比较研究，以进一步了解人类特异性神经病理学。在本研究中，我们报告了一组雄性和雌性黑猩猩（Pan troglodytes）中星形胶质细胞增生、小胶质细胞活化及其与年龄和AD样病理学的关系。黑猩猩与严重的星形胶质细胞增生症表现出广泛的上调肥大的星形胶质细胞的胶质细胞酸性蛋白（GFAP）的免疫反应，在所有层的背外侧前额叶皮层和层间的栅栏的损失。此外，在没有显著小胶质细胞活化和AD病变的情况下，极端星形胶质细胞增生与星形胶质细胞密度增加相关。随着年龄的增长，吞噬性小胶质细胞从静息减少到增加的转变，尽管没有增殖，也没有观察到星形胶质细胞增生的变化。血管淀粉样蛋白与星形胶质细胞和小胶质细胞密度降低相关，而tau蛋白病变与小胶质细胞的形态学变化和更大的总胶质细胞密度和胶质细胞：神经元比率相关。这些结果进一步加深了我们对黑猩猩大脑内炎症过程的理解，并提供了比较数据，以提高我们对人类衰老和神经病理学过程的理解。
Aging and neurodegenerative disorders, such as Alzheimer's disease (AD), trigger an immune response known as glial activation in the brain. Recent evidence indicates species differences in inflammatory responses to AD pathology, highlighting the need for additional comparative studies to further understand human‐specific neuropathologies. In the present study, we report on the occurrence of astrogliosis, microglial activation, and their relationship with age and AD‐like pathology in a cohort of male and female chimpanzees (Pan troglodytes). Chimpanzees with severe astrogliosis exhibited widespread upregulation of hypertrophic astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) throughout all layers of the dorsolateral prefrontal cortex and a loss of the interlaminar palisade. In addition, extreme astrogliosis was associated with increased astrocyte density in the absence of significant microglial activation and AD lesions. A shift from decreased resting to increased phagocytotic microglia occurred with aging, although proliferation was absent and no changes in astrogliosis was observed. Vascular amyloid correlated with decreased astrocyte and microglia densities, while tau lesions were associated with morphological changes in microglia and greater total glia density and glia: neuron ratio. These results further our understanding of inflammatory processes within the chimpanzee brain and provide comparative data to improve our understanding of human aging and neuropathological processes.