Aging in Mice Alters Regionally Enriched Striatal Astrocytes

Authors

Kay E Linker
Violeta Duran-Laforet
Matthias Ollivier
Xinzhu Yu
Dorothy P Schafer
Baljit S Khakh

Publication Date

9-26-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-63429-8

PMID

41006292

PMCID

PMC12475473

PubMedCentral® Posted Date

9-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Aging affects multiple organs and within the brain drives distinct molecular changes across different cell types. The striatum encodes motor behaviors that decline with age, but our understanding of how cells within the striatum change remains incomplete. Using single-cell RNA sequencing from young and aged mice we identify molecularly distinct astrocyte subtypes. We show that astrocytes change significantly with age, exhibiting downregulation of genes, reduced diversity, and a shift to more homogenous inflammatory transcriptomic profiles. By exploring where striatal astrocyte subtypes are located with single-cell resolution, we map astrocytes enriched in dorsal, medial, and ventral striatum. Age increases inflammatory marker transcripts in dorsal striatal astrocytes, which display greater age-related changes than ventral striatal astrocytes. We impute molecular interactions between astrocytes and neurons and find that age particularly reduced interactions related to Nrxn2. Our data show that aging alters regionally enriched striatal astrocytes asymmetrically, with dorsal striatal astrocytes exhibiting greater age-related molecular changes.

Keywords

Animals, Astrocytes, Aging, Mice, Corpus Striatum, Single-Cell Analysis, Male, Mice, Inbred C57BL, Transcriptome, Neurons, Female

Published Open-Access

yes

Recommended Citation

Linker, Kay E; Duran-Laforet, Violeta; Ollivier, Matthias; et al., "Aging in Mice Alters Regionally Enriched Striatal Astrocytes" (2025). Faculty, Staff and Student Publications. 5183.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5183