Brain growth spurt - prenatal ethanol exposure in the guinea pig: Effects on behaviour, cognition and hippocampal function, and comparison with chronic prenatal ethanol exposure.

摘要

Maternal consumption of ethanol during pregnancy can produce a broad spectrum of teratogenic effects. The type and severity of ethanol teratogenicity in the central nervous system (CNS) is dependent on, among other factors, the gestational timing of the ethanol exposure. The developing brain may be especially vulnerable to the teratogenic effects of ethanol exposure during the third-trimester-equivalent, including the brain growth spurt (BGS). It is postulated that suppression of the hippocampal glutamate-N-methyl-D-aspartate (NMDA) receptor-nitric oxide synthase (NOS) signal transduction system in the fetus by chronic prenatal ethanol exposure plays a key role in hippocampal dysmorphology and dysfunction in postnatal life. The main objective of this thesis research was to compare, in the guinea pig, the effects of prenatal ethanol exposure during the BGS versus chronic prenatal ethanol exposure throughout gestation on hippocampal structure and function in the offspring. Prenatal ethanol exposure during the last third of gestation, including the BGS, decreased brain weight, but did not alter spontaneous locomotor activity, the hippocampal glutamate-NMDA receptor-NOS signal transduction system, number of hippocampal CA1 pyramidal cells, spatial learning in the Morris water maze or hippocampal LTP in the CA1 region, all of which were altered by chronic prenatal ethanol exposure. These data indicate that, in the guinea pig, the BGS may not be a critical period of vulnerability for the developing hippocampus to prenatal ethanol exposure for the parameters that were examined. Previous studies in the guinea pig have demonstrated that chronic prenatal ethanol exposure increases the number of gamma-aminobutyric acid type A (GABAA) receptors in the adult cerebral cortex, which may increase the pharmacological sensitivity of this brain region to ethanol, a positive allosteric modulator of the GABA A receptor. An additional objective of this thesis research was to determine in the guinea pig whether chronic prenatal ethanol exposure alters the sensitivity of the brain of the offspring to acute ethanol challenge. In the adult, chronic prenatal ethanol exposure enhanced acute ethanol-induced suppression of cerebral cortical EEG activity selectively in the delta frequency. This electrophysiologic action may contribute to the increased behavioural responsiveness to acute ethanol challenge observed in offspring exposed to ethanol throughout prenatal development.