Prenatal binge-like ethanol exposure induces long-lasting hippocampal oxidative stress, altered inflammatory responses, and memory impairment.

Prenatal ethanol exposure is associated with persistent neurodevelopmental abnormalities, yet the neurobiological consequences of moderate binge-like exposure remain poorly understood. This study investigated whether prenatal ethanol exposure at a moderate binge-drinking dose (3 g/kg/day) during gestational days 6-8 is sufficient to induce persistent oxidative and inflammatory alterations in the hippocampus. In addition, we examined whether these effects emerge early in development (postnatal day 23, shortly after weaning) and persist into adolescence (postnatal day 42). Prenatal ethanol exposure reduced endogenous antioxidant defenses, as evidenced by decreased levels of reduced glutathione and total antioxidant capacity, accompanied by increased lipid peroxidation. This redox imbalance was accompanied by an age-dependent dysregulation of hippocampal inflammatory signaling, characterized at PN23 by increased IL-6 and IL-10 levels and reduced IL-1β and TNF-α levels, followed at PN42 by increased IL-1β and TNF-α and reduced IL-6 and IL-10 relative to PN23. Behavioral assessments revealed impairments in both spatial and working memory, demonstrated by poorer performance in the Morris water maze and reduced spontaneous alternation behavior in the Y-maze. Factorial analyses indicated that treatment effects were largely consistent between males and females across biochemical, inflammatory, and behavioral outcomes. However, sex-dependent treatment effects were identified for specific measures of long-term spatial memory, including a significant Treatment × Sex interaction for time spent in the target quadrant and a significant treatment × sex × age interaction for latency to first enter the target quadrant. Taken together, these findings demonstrate that moderate prenatal binge-like ethanol exposure is sufficient to induce persistent hippocampal redox imbalance and inflammatory dysregulation, contributing to long-lasting impairments in spatial and working memory. These results provide further evidence that even moderate prenatal ethanol exposure can produce enduring neurobiological and cognitive consequences extending into adolescence.