Unique signatures of stress-induced senescent human astrocytes.

Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Sep 16;:113466 Authors: Simmnacher K, Krach F, Schneider Y, Alecu JE, Mautner L, Klein P, Roybon L, Prots I, Xiang W, Winner B Abstract Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes which comprises dysregulated pathways. Both, senescent and reactive human astrocytes activated a pro-inflammatory pattern. Astrocyte senescence was at least partially depending on active mechanistic-target-of-rapamycin (mTOR) and DNA-damage-response signaling, both drivers of senescence. To further investigate how PD and senescence connect to each other, we asked if a PD-linked environmental factor induces senescence and if senescence impairs midbrain neurons. We could show that the PD-linked pesticide rotenone causes astrocyte senescence. We further delineate, that the senescent secretome exaggerates rotenone-induced neurodegeneration ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research