Dietary choline-derived Trimethylamine N-oxide impairs hippocampal neuronal function via PANoptosis activation.

ABSTRACT: The gut microbial metabolite Trimethylamine N-oxide (TMAO) is increasingly implicated in the functioning and pathology of the central nervous system. Here, we demonstrate that chronic systemic TMAO exposure in mice induces significant cognitive impairment, as shown by significant deficits across multiple metrics in a battery of behavioral tests, including the novel object recognition, Y-maze, and Morris water maze (p < 0.05). This behavioral deficit was associated with severe hippocampal neurodegeneration, including a 20.5% loss of pyramidal neurons in the CA1 subregion, and marked mitochondrial damage. Mechanistically, TMAO-induced neurotoxicity was driven by PANoptosis, a coordinated inflammatory cell death pathway. We observed robust activation of the sensor ZBP1 and downstream executio

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12624029 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature