Paraquat induced depression-related neurobehavioral abnormalities in zebrafish: Linkage between hepatic SAM...

Accumulating epidemiological and toxicological evidence implicates the herbicide paraquat (PQ) as an environmental risk factor for depressive neuropsychiatric disorders. In this study, we demonstrated that PQ exposure induces depression-associated neurobehavioral abnormalities in adult zebrafish. Subsequent examination revealed that chronic PQ exposure markedly suppressed hepatic biosynthesis of S-adenosylmethionine (SAM), selectively downregulated methyltransferase METTL16 expression, and reduced global cerebral N⁶-methyladenosine (m⁶A) abundance. Integrative analyses combining cerebral MeRIP-seq and transcriptome sequencing data further identified pervasive perturbations in the m⁶A epitranscriptomic landscape and transcriptional profiles of functional genes enriched in synaptic plasticity, neurotransmission and depression-associated signaling cascades. Notably, exogenous SAM supplementation effectively ameliorated impaired brain m⁶A methylation and PQ-evoked depression-related behavioral phenotypes. Collectively, our findings support inter‑organ crosstalk linking impaired hepatic SAM metabolism to reduced cerebral m⁶A abundance. The consequent epitranscriptomic disruption underpins PQ-associated neurobehavioral abnormalities, pointing to SAM as a promising candidate therapeutic agent against depressive disorders induced by environmental toxicants.