Temporal Profiling of Male Cortical Astrocyte Transcription Predicts Molecular Shifts From Early Development to Aging.

Abstract

Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrating remarkable morphological structural complexity, which is attained in the second postnatal month. Throughout this period of development and across the remainder of the lifespan, astrocytes participate in CNS homeostasis, support neuronal partners, and contribute to nearly all aspects of CNS function. In the present study, we analyzed astrocyte gene expression in the cortex of wild-type male rodents throughout their lifespan (postnatal 7 days to 18 months). A pairwise timepoint comparison of differential gene expression during early development and CNS maturation (7-60 days) revealed four unique astrocyte gene clusters, each with hundreds of genes, which demonstrate unique temporal profiles. These clusters are distinctively related to cell division, cell morphology, cellular communication, and vascular structure and regulation. A similar analysis across adulthood and in the aging brain (3 to 18 months) identified similar patterns of grouped gene expression related to cell metabolism and cell structure. Additionally, our analysis identified that during the aging process astrocytes demonstrate a bias toward shorter transcripts, with loss of longer genes related to synapse development and a significant increase in shorter transcripts related to immune regulation and the response to DNA damage. Our study highlights the critical role that astrocytes play in maintaining CNS function throughout life and reveals molecular shifts that occur during development and aging in the cortex of male mice.