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

Quick Facts

  • Publication title: DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains
  • Journal: Aging Cell
  • Year: 2025
  • DOI: 10.1111/acel.70228
  • PMID/PMCID: 40974022; PMC12610410

Research overview

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. Our findings reveal a systemic mechanism underlying the sustained activation of microglia following brain aging, paving the way for improving chronic neuroinflammation, cellular senescence, and cognitive decline associated with aging.

Key findings

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 levels, which subsequently leads to sustained DP1 signaling activation.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification.

Related platforms: Exoomics®

Related services and capabilities: Tissue EV Isolation & Purification

References

Original publication: DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains Aging cell. 2025. DOI: 10.1111/acel.70228. PMID/PMCID: 40974022; PMC12610410.