DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains.

ABSTRACT: Aging leads to neurodegenerative diseases, such as cognitive decline, which are induced by persistent chronic low-grade inflammation in the brain driven by microglial activation. However, whether and how brain-derived exosomes from aged mice (A-exo) induce a pro-inflammatory state and cellular senescence in microglia within the aging brain is poorly understood. Here, we report that brain-derived exosomes from aged mice (A-exo) cause cognitive decline in normal young mice, inducing microglial overactivation, lipid droplet accumulation, and senescence-associated secretory phenotype (SASP) secretion. This abnormal microglial activity arises from the elevated expression of PTGDS in A-exo due to mouse aging, resulting in increased central and peripheral D-prostanoid receptor 1 (DP1) ligand PGD2

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12610410 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature