Senescent Phenotype of Astrocytes Leads to Activation of BV2 Microglia and N2a Neuronal Cells Death

星形胶质细胞的衰老表型导致 BV2 小胶质细胞的激活和 N2a 神经元细胞的死亡

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作者:Wenyou Zhang, Xuehan Yang, Jingyue Liu, Yichen Pan, Ming Zhang, Li Chen

Background

Astrocytes, the most abundant cell type in the central nervous system, are essential to tune individual-to-network neuronal activity. Senescence in astrocytes has been discovered as a crucial contributor to several age-related neurological diseases. Here, we

Conclusions

Senescent astrocyte might affect neurons directly or indirectly acting on the regulation of normal and pathological brain aging.

Methods

In vivo, mice were housed for four, 18, and 26 months. An in vitro cell model of aged astrocytes was constructed by serial passaging until passage 20-25, and those within 1-5 were invoked as young astrocytes. Meanwhile, an oxidative induced astrocyte senescence model was constructed by H2O2 induction. (3)

Results

In vitro aged astrocytes all showed manifest changes in several established markers of cellular senescence, e.g., P53, P21, and the release of inflammatory cytokine IL-6 and SA-β-gal positive cells. Results also showed mitochondrial dysfunction in the oxidative stress-induced astrocyte senescence model and treatment of berberine could ameliorate these alterations. Two types of senescent astrocytes' conditioned medium could impact on neuron apoptosis in direct or indirect ways. (4) Conclusions: Senescent astrocyte might affect neurons directly or indirectly acting on the regulation of normal and pathological brain aging.

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