Spatial transcriptomics of the aging mouse brain reveals origins of inflammation in the white matter.

ABSTRACT: To systematically understand age-induced molecular changes, we performed spatial transcriptomics of young, middle-aged, and old mouse brains and identified seven transcriptionally distinct regions. All regions exhibited age-associated upregulation of inflammatory mRNAs and downregulation of mRNAs related to synaptic function. Notably, aging white matter fiber tracts showed the most prominent changes with pronounced effects in females. The inflammatory signatures indicated major ongoing events: microglia activation, astrogliosis, complement activation, and myeloid cell infiltration. Immunofluorescence and quantitative MRI analyses confirmed physical interaction of activated microglia with fiber tracts and concomitant reduction of myelin in old mice. In silico analyses identified potential t

SUBMITTER: Wang L 

PROVIDER: S-EPMC11971433 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature