Maternal oxytocin mitigates offspring autism-like phenotypes and oxytocin system alterations through improved...

Maternal care is crucial for normal neurodevelopment. Disruptions in early caregiver-infant interactions, potentially linked to modern lifestyles, may contribute to the rising prevalence of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Given the reported deficits in the oxytocinergic system in both ASD and impaired mother-child interactions, this study investigated: (1) whether inadequate maternal care induced by early-life maternal separation (MS) in female rats leads to autism-like phenotypes in their offspring, and (2) whether improving maternal care with oxytocin (OXT) can ameliorate these outcomes. Female rat pups underwent MS (3 h/day from postnatal day (PND) 1-14). As adults, they were mated and assigned to MS+Saline, MS + OXT (0.8 IU/kg intranasal, PND1-14), or control groups. Maternal behavior was assessed. Their male offspring were evaluated during adolescence for social and repetitive behaviors, and their brains were analyzed for hypothalamic OXT and hippocampal Oxytocin Receptors (OXTRs) expression. Dams with a MS history exhibited impaired maternal care, characterized by reduced nursing and increased harmful behaviors. OXT treatment significantly improved maternal care in these dams. The offspring of MS+Saline dams displayed core autism-like phenotypes, including social deficits and increased repetitive behaviors, alongside reduced OXT expression in the hypothalamus and OXTR expression in the hippocampus. Crucially, these behavioral and neurobiological abnormalities were ameliorated in the offspring of OXT-treated MS dams. This study demonstrates that impaired maternal care, resulting from early-life stress, can induce autism-like abnormalities in offspring. OXT administration to dams effectively improves maternal behavior and mitigates the development of these abnormalities, highlighting the maternal environment as a key modifiable factor. Our findings provide a compelling preclinical framework supporting the potential of early interventions focused on the parent-child environment to mitigate neurodevelopmental risk.