The Effects of IL-1β on Astrocytes are Conveyed by Extracellular Vesicles and Influenced by Age.

The aging brain is associated with significant pathophysiological changes reflected in changes in astrocyte function. In this study, we hypothesized that the response of astrocytes to mechanical and inflammatory stimulation would differ with long-term culture. We report that naïve short-term cultured (young) and long-term cultured astrocytes (aged) exhibit similar recovery to a scratch wound assay. However, in response to IL-1β young astrocytes have an arrested recovery which is not observed in IL-1β treated aged astrocytes. We had recently reported that astrocytes release extracellular vesicles (EVs) in response to IL-1β treatment. Given the disparate phenotypes between young and aged astrocytes, we next examined whether the EVs released from astrocytes reflected the differences in cellular responses to scratch and IL-1B treatment. Young cultures challenged with EVs collected from IL-1β treated cells exhibited a robust inhibition of wound recovery when compared to astrocytes treated with EVs collected from IL-1β treated aged astrocyte cultures. Heterochronic experiments also determined that the effect of IL-1β on astrocyte scratch wound recovery could be recapitulated by EVs alone. Taken together, these findings provide new information on how senescence alters the functional response and how EVs from astrocytes may elicit changes in glial responses which may have relevance to understanding neurological diseases.