Postnatal immune activation and adult affective vulnerability: Behavioral and glial outcomes in rodent models - A systematic review.

BACKGROUND

Anxiety and depression are highly prevalent, early-onset disorders. Converging evidence suggests that glial cells play a key role in mediating the effects of early-life immune activation, acting as a long-term programming factor for later-life emotional dysregulation.

OBJECTIVE

This systematic review synthesized the enduring long-term outcomes of postnatal immune challenge on social behavior and on anxiety- and depression-like behaviors in rodent models, along with glial reactivity and morphology.

METHODS

Following PRISMA 2020 guidelines, studies published between 2015 and 2025 were screened; 21 met the inclusion criteria. Most studies utilized LPS (86%) administered between PND 2-15. Methodological quality was predominantly moderate (57%) or high (38%).

RESULTS

Behavioral outcomes: social deficits were reported in 83% of the studies and depression-like phenotypes in 73%, whereas anxiety-like behavior exhibited greater variability and was often modulated by sex. Microglial activation markers were altered in most of the studies; however, glial morphological changes were documented in only half of the studies. Increased astrocytic GFAP expression, particularly in hippocampal and prefrontal regions, was reported in 29% of studies, and astrocyte morphology was rarely quantified. Sex-dependent effects were reported in a subset of studies with a tendency toward male-biased vulnerability in anxiety and social domains.

CONCLUSION

The available preclinical evidence supports an association between early postnatal immune activation and increased affective vulnerability across post-weaning stages, frequently accompanied by persistent microglial remodeling. Heterogeneity in timings, dose, and sex-specific responses limits mechanistic inference, underscoring the need for standardized, sex-balanced, developmentally-stratified designs and more extensive investigation into astrocytic contributions to neuroimmune programming.