# Early-life stress and inflammation: A systematic review of a key experimental approach in rodents

## TL;DR

This study reviews how early-life stress in rodents affects inflammation and immune responses, especially when combined with later-life stress.

## Contribution

The study systematically reviews the effects of repeated maternal separation on inflammatory markers and microglia in rodents.

## Key findings

- Repeated maternal separation leads to short-term pro-inflammatory effects in various tissues when combined with later-life stress.
- Animals with repeated maternal separation show increased microglial activation and cytokine signaling in brain regions linked to psychiatric disorders.
- Early-life stress alone does not cause long-term inflammation unless combined with later-life stress.

## Abstract

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.