Unidad Periférica de Neurociencias, Instituto Nacional de Neurología y Neurocirugía/Universidad Nacional Autónoma de México. Av. Insurgentes Sur No. 3877 Col. La Fama, Tlalpan, C.P. 14269, Ciudad de México, Mexico.
Departamento de Biología Celular, CINVESTAV-IPN, Av. Instituto Politécnico Nacional No. 2508, Col. San Pedro Zacatenco, Gustavo A. Madero, C.P. 07360, Ciudad de México, Mexico.
Int J Mol Sci. 2020 Mar 14;21(6):1983. doi: 10.3390/ijms21061983.
One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer's disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD.
大脑老化过程的特征之一是存在慢性炎症反应，这种炎症反应在神经退行性变中尤为明显。另一方面，已经证明芳基烃受体（AHR）参与了炎症反应。目前，动物模型的证据表明，衰老的特征与 AHR 水平的变化有关。然而，关于 AHR 在人类衰老大脑或阿尔茨海默病（AD）中的行为和参与，目前还没有信息。我们通过免疫组织化学评估了人类海马体死后组织中 AHR 的表达及其与反应性星形胶质细胞的关系。此外，我们通过 ELISA 分析了来自年轻和年长参与者以及 AD 患者的血清中 AHR 水平。与年轻的死后脑组织样本相比，年长的死后脑组织样本中的 AHR 和神经胶质纤维酸性蛋白水平更高。AHR 主要定位于星形胶质细胞的细胞质中，并呈现出类似于细胞外囊泡的模式；这种特征在 AD 患者中更为明显。我们发现 AD 患者的血清 AHR 水平高于其他参与者。这些结果表明，AHR 参与了衰老过程，可能也参与了 AD 等神经退行性疾病的发展。
