Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged...

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Early-life stress (ELS) increases susceptibility to psychiatric disorders like depression.
• Neuroinflammation is linked to ELS, but its effect on microglia, the CNS immune cells, is unclear.

Purpose of the Study:

• To investigate the impact of ELS on microglial morphology, gene expression, and phagocytic capacity.
• To determine if ELS-induced microglial changes persist into adulthood and are relevant to human child abuse.

Main Methods:

• ELS was induced in mice using limited nesting material (postnatal days 2-9).
• Microglial morphology, hippocampal gene expression, and synaptosome phagocytosis were assessed at postnatal day 9 (P9) and P200.
• Gene expression changes were analyzed, and in situ hybridization was used to examine GAS6 expression in human brain samples.

Main Results:

• ELS altered microglial morphology and gene expression (TNF response, ubiquitination) in adult mice.
• Microglial phagocytic capacity for synaptosomes was reduced in adult ELS mice.
• ELS induced distinct microglial gene expression profiles during development and in response to LPS challenge.
• Increased GAS6 expression, a phagocytosis-related gene, was observed in ELS mice and in humans with a history of child abuse.

Conclusions:

• ELS causes lasting changes in microglial function, including impaired phagocytosis.
• Altered microglial phagocytic capacity is a significant factor in ELS-induced psychiatric vulnerability.
• These findings highlight microglia as a potential therapeutic target for ELS-related disorders.