Prenatal ethanol exposure induces long-term hippocampal AMPAergic dysfunction

Ethanol (EtOH) exposure during pregnancy can induce a range of physical, learning, and behavioral disorders in the newborn clinically referred as Fetal Alcohol Spectrum Disorder (FASD). Unfortunately, FASD is poorly understood, and the underlying mechanisms are not fully known. Here, we studied the role of AMPA receptors (AMPARs) in in vitro and in vivo models of prenatal alcohol exposure (PAE). For the in vitro study, immature rat organotypic hippocampal slices were exposed to EtOH (150 mM) for 7 days followed by 24 hours of withdrawal. For the in vivo study, female C57/Bl6 mice were exposed to 10% EtOH during the first trimester of pregnancy and the offspring were analysed from birth to adolescence to study growth curves, facial dysmorphology, as well as biomolecular, electrophysiological and behavioural parameters. Our in vitro results show that chronic EtOH exposure and 24 hours of withdrawal induces a significant reduction in AMPARs expression and function and alteration of neuronal circuits (Gerace et al., 2023). Similar results were obtained in adolescent PAE litters. Indeed, these animals show a significant reduction of the AMPAergic response, associated with altered expression of excitatory synaptic proteins in postsynaptic compartments. Our molecular and functional results may be associated to the behavioural alterations observed in PAE offspring, which display reduced object recognition without alteration in locomotor activity. Our study suggest that PAE leads to a dysfunction of AMPAergic neurotransmission that may lead to neurodevelopmental impairments and could aid in the comprehension of the pathogenesis of FASD.