Prenatal ethanol intoxication and maternal intubation stress alter cell survival and apoptosis in the postnatal development of rat hippocampus

Abstract

It is well known that the fetal ethanol exposure and prenatal stress may have adverse effects on brain development. Interestingly, some morphological and functional recovery from their teratogenic effects that take place during brain maturation. However, mechanisms that underlie this recovery are not fully elucidated. The aim of this study was to examine whether the postnatal attenuation of fetal alcohol -and maternal stress-induced morphological and functional deficits correlates with compensatory changes in the expression/activation of the brain proteins involved in inflammation, cell survival and apoptosis. In this project, we investigated the hippocampus which belongs to the brain regions most susceptible to the adverse effects of prenatal ethanol exposure. Pregnant rat dams were administered ethanol (A) or isocaloric glucose solution (IC) by a gastric intubation during gestational days 7-20. The pure control group received ad libitum laboratory chow and water with no other treatment. The hippocampi of fetal-ethanol and control pups were examined at the postnatal day (PD)1, PD10, PD30 and PD60. Moderate fetal-ethanol exposure and prenatal intubation stress caused a significant increase in molecular factors relating to inflammation (iNOS) and cell survival/apoptosis pathways (PTEN, GSK-3 and ERK) at birth, with a rapid compensation from these developmental deficits upon removal of alcohol at PD10. Indeed, an increase in ERK1/2 and JNK1/2 activation at PD30 was observed with ethanol consumption. It indicates that the recovery process in A and IC brains started soon after the birth upon the ethanol and stressor withdrawal and continued until the adulthood.

Alcohol use in pregnancy and its impact on the mother and child

“…In large‐scale epidemiological studies, children of mothers with an alcohol‐related diagnosis during pregnancy (suggesting more than moderate alcohol consumption), have a threefold risk of cerebral palsy [110]. The relationship between any prenatal alcohol exposure and cerebral palsy is difficult to establish as neither can be reliably diagnosed until a child is older [111] but in animal models, alcohol exposure may lead to a general fetal inflammatory response [112] and oxidative stress [113] that may affect neuronal survival especially in key parts of the brain, such as the hippocampus [112]. Dietary modulation may offer some potential in mitigating prenatal neurological injury associated with alcohol [113].…”