Postnatal depression-associated breastmilk extracellular vesicles mediate intergenerational effects on offspring neurodevelopment.

Maternal postnatal depression is linked to offspring hippocampal dentate gyrus neuron maturation defects, producing cognitive deficits and depressive-like behaviors in cross-fostering models.

• Why it matters: The mechanism linking maternal postnatal depression to offspring neurodevelopmental impairments is unclear, limiting therapeutic strategies to interrupt intergenerational transmission.
• What they did: Cross-fostering showed disrupted newborn neuron maturation in offspring hippocampal dentate gyrus after maternal depression; gastric dosing with PND-derived breastmilk sEVs recapitulated phenotypes, implicating sEV miRNAs.
• The result: PND-induced breastmilk sEV miRNAs suppress mGluR8 in supramammillary nucleus neurons projecting to DG, driving a “high-frequency, low-amplitude” activation pattern; blocking mammary sEV secretion or sequestering these miRNAs rescues deficits.