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Early-life stress impacts the adult microglia transcriptome under basal and inflammatory conditions

ABSTRACT: Early-life stress (ELS) leads to increased vulnerability to psychiatric illness including cognitive impairment later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but, how ELS impacts microglia, the macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (P2 – P9) on the morphology and gene expression of microglia from young (postnatal day (P)9) and adult (P200) mice. ELS led to a change in the proportion of morphological microglia subtypes in adulthood, associated with immune reactivity. At the transcriptional level, whereas at P9 no ELS mediated changes were detected, at P200 ELS induced transcriptional changes in microglia genes involved in the immune response and protein ubiquitination. Additionally, ELS altered microglia gene expression changes during development from P9 to P200 and in response to LPS at P200, in both cases marked by GO-terms associated with the immune response. Concluding, these data show that ELS has persistent effects on the morphology and gene expression program of microglia and results in an altered transcriptional response to a systemic LPS challenge.

ORGANISM(S): Mus musculus

PROVIDER: GSE207067 | GEO | 2022/12/14

REPOSITORIES: GEO

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