Fetal Alcohol Syndrome Research Today is a free monthly online journal that collates and summarizes the latest research about Fetal Alcohol Syndrome, including details on pregnancy, birth defects, causes, symptoms, treatment. | ||||||||
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Reversal of alcohol-induced learning deficits in the young adult in a model of fetal alcohol syndrome.Incerti M, Vink J, Roberson R, Wood L, Abebe D, Spong CY Unit on Perinatal and Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-0925, USA. maddalena.incerti@gmail.com 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 gamma-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, GABAAbeta3, GABAAalpha5, 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. Published 22 January 2010 in Obstet Gynecol, 115(2): 350-6.
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