title: Neurotrophic peptides, ADNF-9 and NAP, prevent alcohol-induced apoptosis at midgestation in fetal brains of C57BL/6 mouse.
abstract: Prenatal alcohol exposure is known to induce fetal brain growth deficits at different embryonic stages. We focused this study on investigating the neuroprotective effects against alcohol-induced apoptosis at midgestation using activity-dependent neurotrophic factor (ADNF)-9, a peptide (SALLRSIPA) derived from activity-dependent neurotrophic factor, and NAP, a peptide (NAPVSIPQ) derived from activity-dependent neuroprotective protein. We used an established fetal alcohol exposure mouse model. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) group with 25 % (4.49 %, v/v) ethanol-derived calories, (2) pair-fed (PF) control group, (3) ALC combined with i.p. injections (1.5 mg/kg) of ADNF-9 (ALC/ADNF-9) group, (4) ALC combined with i.p. injections (1.5 mg/kg) of NAP (ALC/NAP) group, (5) PF liquid diet combined with i.p. injections of ADNF-9 (PF/ADNF-9) group, and (6) PF liquid diet combined with i.p. injections of NAP (PF/NAP) group. On day 15 (E15), fetal brains were collected, weighed, and assayed for TdT-mediated dUTP nick end labeling (TUNEL) staining. ADNF-9 or NAP was administered daily from E7 to E15 alongside PF or ALC liquid diet exposure. Our results show that NAP and ADNF-9 significantly prevented alcohol-induced weight reduction of fetal brains. Apoptosis was determined by TUNEL staining; NAP or ADNF-9 administration alongside alcohol exposure significantly prevented alcohol-induced increase in TUNEL-positive cells in primordium of the cingulate cortex and ganglionic eminence. These findings may pave the path toward potential therapeutics against alcohol intoxication during pregnancy stages.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614, USA. youssef.sari@utoledo.edu
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
authors.forename: Jason M
authors.initials: JM
authors.lastname: Weedman
authors.forename: Maxwell
authors.initials: M
authors.lastname: Nkrumah-Abrokwah
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011247:Pregnancy
chemical_list: D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; D000431:Ethanol; C425904:davunetide