Repository logo
 

Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Willis, Cory M 
Nicaise, Alexandra M  ORCID logo  https://orcid.org/0000-0001-7160-5988
Bongarzone, Ernesto R 
Givogri, Maria 
Reiter, Cory R 

Abstract

The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain.

Description

Keywords

Aging, Animals, Astrocytes, Brain, Cell Differentiation, Cells, Cultured, Cellular Senescence, Extracellular Vesicles, Mice, Oligodendroglia, Proteomics

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

10

Publisher

Springer Science and Business Media LLC