Microglial memory of early life stress and inflammation: susceptibility to neurodegeneration in adulthood

TL;DR

This review explores how early life stress and inflammation influence microglial memory, increasing susceptibility to neurodegeneration in adulthood, and discusses potential early biomarkers and interventions.

Contribution

It synthesizes current evidence on microglial memory's role in neurodegeneration and proposes future research directions for early detection and intervention.

Findings

Microglial polarization is affected by early life stress and inflammation.

Microglial memory may serve as an early biomarker for neurodegeneration.

Potential for early life interventions to modify disease trajectories.

Abstract

We review evidence supporting the role of early life programming in the susceptibility for adult neurodegenerative diseases while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to neurodegeneration. We review the mediating mechanisms which may function as early biomarkers of increased susceptibility for neurodegeneration. Can we devise novel early life-modifying interventions to steer developmental trajectories to their optimum?