Gestational choline supplementation regulates hippocampal granule neuron development and emotion-like behavior

Prenatal nutrition can profoundly influence the brain development of offspring through mechanisms including epigenetic reprogramming. However, the complex interplay of maternal nutrition, neural development, and behaviors at the cellular level remains to be explored. Here, we report that gestational choline supplementation (GCS) in mice attenuates anxiety- and depression-like behaviors in male offspring (F1_GCS). Multi-omics analysis reveals the comprehensive roles of GCS in diverse aspects of neuronal functions in F1_GCS. Notably, the transcriptome, intercellular communication, and chromatin accessibility of immature granule neurons were altered in the hippocampus of F1_GCS. This was accompanied by enhanced transcription and increased chromatin accessibility in glutamate signaling and suppressed transcription and reduced chromatin accessibility in MIF pathways in these neurons. Correlation analysis of cell populations with neuropsychiatric disorders showed a strong association between immature granule neurons and emotional disorders. Together, these findings provide molecular and cellular evidence supporting the effects of a widely used nutritional supplement in nutritional interventions.