OBJECTIVE: To evaluate whether treatment with neuroprotective peptides to young adult mice prenatally exposed to alcohol reverses alcohol-induced learning deficits in a mouse model of fetal alcohol syndrome, whether the mechanism involves the N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid type A (GABAA) receptors, and whether it is related to glial cells. METHODS: C57Bl6/J mice were treated with alcohol (0.03 ml/g) or placebo on gestational day 8. On day 40, male mice exposed to alcohol in utero were treated daily for 10 days with D-NAPVSIPQ and D-SALLRSIPA (n=20) or placebo (n=13); and control offspring were treated with placebo (n=46), with the treatment blinded. Learning evaluation began after 3 days using the Morris watermaze and the T-maze. The hippocampus, cortex, and cerebellum were isolated. Expression of NR2A, NR2B, GABAAβ3, GABAAα5, vasoactive intestinal peptide (VIP), activity-dependent neuroprotective protein, and glial fibrillary acidic protein was measured using calibrator-normalized relative real-time polymerase chain reaction. Statistical analysis included analysis of variance and Fisher's protected least significant difference. Results: Treatment with D-NAPVSIPQ and D-SALLRSIPA reversed the alcohol-induced learning deficit in both learning tests as well as the NR2A and NR2B down-regulation in the hippocampus and the up-regulation of NR2A in the cortex and NR2B in the cortex and cerebellum (all P<.05). No significant differences were found in GABAA expression. Moreover, the peptides changed activity-dependent neuroprotective protein expression in the cortex (P=.016) but not the down-regulation of VIP (P=.883), probably because the peptides are downstream from VIP. Conclusion: Alcohol-induced learning deficit was reversed and expression of NR2A and NR2B was restored in the hippocampus and cortex of young adult mice treated with D-NAPVSIPQ and D-SALLRSIPA. Given the role of NMDA receptors in learning, this may explain in part the mechanism of prevention of alcohol-induced learning deficits by D-NAPVSIPQ and D-SALLRSIPA.
ASJC Scopus subject areas
- Obstetrics and Gynecology