Cumulative environmental exposures adversely impact social behaviour and are associated with dysregulation of genes and proteins involved in epigenetic, ribosomal, and immune regulation in male mice.

ABSTRACT:

Objective

This study investigated how cumulative environmental exposures influence offspring behaviour and inflammation-related molecular signatures in the brain and peripheral immune system.

Methods

A novel "triple-hit" mouse model was developed using C57Bl/6JAusB mice (N = 70), combining preconceptual social stress, antenatal high-fat diet, and a postnatal immune challenge (poly(I:C), 10 mg/kg). At 12 weeks, offspring underwent behavioural tests relevant to neurodevelopmental disorders (NDDs), including the Elevated Plus Maze, 3-Chamber Social Preference, Self-Grooming, and Marble Burying. A composite NDD-risk index was calculated. Single-cell RNA sequencing (scRNA-seq) and bulk proteomics were performed on male triple-hit offspring to identify differentially expressed gen

SUBMITTER: Bucknor MC 

PROVIDER: S-EPMC12783315 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature