Treatment with Neuropeptides Attenuatesc-fosExpression in a Mouse Model of Fetal Alcohol Syndrome

Abstract

Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation and is characterized by neurodevelopmental anomalies. C-FOS is a cellular marker of transcriptional activity in the stress-signal pathway. Previously, we showed the treatment with NAP (NAPVSIPQ) + SAL (SALLRSIPA) reversed the learning deficit after prenatal alcohol exposure in FAS. Our objective was to evaluate if the mechanism of actions of NAP + SAL involves the stress-signal pathway differentiating C-FOS expression in mouse brains after prenatal alcohol exposure. C57Bl6/J mice were treated with alcohol (0.03 mL/g) or placebo on gestational day 8. On postnatal day 40, in utero alcohol-exposed males were treated via gavage with 40 μg D-NAP and 40 μg D-SAL ( N = 6) or placebo ( N = 4); controls were gavaged with placebo daily ( N = 12). After learning evaluation, hippocampus, cerebellum, and cortex were isolated. Calibrator-normalized relative real-time polymerase chain reaction and Western blot analysis were performed. Statistics included analysis of variance and post hoc Fisher analysis. Adult treatment with NAP + SAL restored the down-regulation of C-FOS in the hippocampus after prenatal alcohol exposure ( P < 0.05), but not in the cerebellum. There was no difference in C-FOS expression in the cortex. Adult treatment with NAP + SAL restored the down-regulation of C-FOS expression in hippocampus attenuating the alcohol-induced alteration of the stress-signal pathway.