title: Treatment with neuropeptides attenuates c-fos expression 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.
authors.affiliation: Unit on Perinatal and Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-0925, USA. maddalena.incerti@gmail.com
authors.forename: Maddalena
authors.initials: M
authors.lastname: Incerti
authors.forename: Joy
authors.initials: J
authors.lastname: Vink
authors.forename: Robin
authors.initials: R
authors.lastname: Roberson
authors.forename: Daniel
authors.initials: D
authors.lastname: Abebe
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007223:Infant; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000627:therapeutic use; D009479:Neuropeptides / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C526732:SALLRSIPA; D000431:Ethanol