Effects of chronic prenatal ethanol exposure on glutamate release and cGMP content in the hippocampus of the young postnatal guinea pig.

摘要

Fetal alcohol (ethanol) exposure can result in central nervous system (CNS) teratogenicity that can manifest as the fetal alcohol syndrome in humans, in which there are persistent behavioural and cognitive deficits throughout postnatal life. Behaviour, learning and memory are controlled, in part, by the hippocampus and its excitatory glutamate signaling system. This research was designed to determine the effects of chronic prenatal ethanol exposure (CPEE) on glutamate release and cGMP content in young postnatal guinea pig offspring. In the first study, the hypotheses tested in the postnatal day (PD) 12 guinea pig hippocampus were that CPEE (1) decreases glutamate release, and (2) increases the inhibitory effect of acute in vitro ethanol exposure on stimulated glutamate release. In the second study, we extended our initial findings by testing the hypothesis that CPEE decreases glutamate release and cGMP content in the hippocampus of younger (PD 1 and PD 5) offspring. Timed, pregnant guinea pigs were treated daily throughout gestation with 4 g ethanol/kg maternal body weight, isocaloric-sucrose/pair-feeding, or water. CPEE had no effect on body weight, but decreased brain and hippocampal weights in PD 1, 5, and 12 offspring (p < 0.05), and increased spontaneous locomotor activity at PD 12 (p < 0.05). K+- and veratridine-stimulated glutamate release in hippocampal slices of PD 12 offspring was decreased by CPEE (p < 0.05), but CPEE did not increase the sensitivity of K +-stimulated glutamate release to inhibition by acute in vitro exposure to 50 mM ethanol. CPEE did not affect K+-stimulated glutamate release at PD 1 or PD 5, whereas CPEE decreased NMDA-stimulated glutamate release at PD 5 (p < 0.05), but not PD 1. CPEE decreased 60 mM K +-stimulated hippocampal cGMP content at PD 1 (p < 0.05), whereas at PD 5, CPEE increased 60 mM K+-stimulated cGMP content (p < 0.05). This thesis demonstrates that CPEE perturbs the glutamate signaling pathway of the hippocampus during early postnatal life, which may contribute to the cognitive and behavioural deficits of ethanol CNS teratogenicity.