ACSS2 plays a role in mediating lasting transcriptomic dysregulation in the dorsal hippocampus and cerebellar vermis of mice chronically prenatally exposed to alcohol

ABSTRACT: BACKGROUND: Recent findings showed that alcohol-derived acetate contributes to ACSS2-dependent histone acetylation in the brain, and this metabolic-epigenetic mechanism regulates alcohol-associated learning. Further, alcohol-derived acetate is incorporated into histone acetylation in gestating fetal brains following acute maternal alcohol exposure in late pregnancy (E18.5). GOAL: Determine any role of ACSS2 in mediating chronic prenatal alcohol exposure (cPAE)-driven lasting transcriptomic effects in the brain. APPROACH: We used RNA sequencing to investigate the lasting cPAE-related transcriptomic effects in the dorsal hippocampus (dHPC) and cerebellar vermis of adolescent WT and ACSS2 KO mice. These two brain regions were selected because of their implications in hallmark FASD phenotypes (long-term memory impairments and motor deficits, respectively). The chronic prenatal exposure model was a daily i.p. injection (3 g/kg ethanol or equivalent volume saline) to pregnant dams from E0.5 until pups were born. FINDINGS: cPAE resulted in lasting gene and transcript expression changes in both of these brain regions of both genotypes compared to respective saline (cPSE)-treated controls. There were few enriched biological processes, indicating cPAE has widespread lasting transcriptomic effects across a variety of pathways. cPAE-related differentially expressed features (DEFs: DEGs and DETs) were nearly entirely specific to genotype, evidenced by very few DEFs overlapping between genotypes. All but one of these overlapping DEFs were oppositely affected between genotypes. Further, there were hundreds of DEFs exhibiting significant interaction between genotype and prenatal exposure. Taken together, these findings suggest that lasting cPAE-related transcriptomic dysregulation is in part modulated by ACSS2.

ORGANISM(S): Mus musculus

PROVIDER: GSE310211 | GEO | 2026/03/09

REPOSITORIES: GEO