Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice.

ABSTRACT: Diet-related maternal obesity has been implicated in neurodevelopmental disorders in progeny. Although the precise mechanisms and effective interventions remain uncertain, our research elucidates some of these complexities. We established that a prenatal high-fat diet triggered maternal immune activation (MIA), marked by elevated serum lipopolysaccharide levels and inflammatory-cytokine overproduction, which dysregulated the maternal tryptophan metabolism promoting the accumulation of neurotoxic kynurenine metabolites in the embryonic brain. Interventions aimed at mitigating MIA or blocking the kynurenine pathway effectively rescued the male mice social performance. Furthermore, excessive kynurenine metabolites initiated oxidative stress response causing neuronal migration deficits in the

SUBMITTER: Sun P 

PROVIDER: S-EPMC11873046 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature