Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol.
BACKGROUND
A derived peptide from activity-dependent neurotrophic factor (ADNF-9) has been shown to be neuroprotective in the fetal alcohol exposure model. We investigated the neuroprotective effects of ADNF-9 against alcohol-induced apoptosis using TUNEL staining. We further characterize in this study the proteomic architecture underlying the role of ADNF-9 against ethanol teratogenesis during early fetal brain development using liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS).


METHODS
Pregnant C57BL/6 mice were exposed from embryonic days 7-13 (E7-E13) to a 25% ethanol-derived calorie [25% EDC, Alcohol (ALC)] diet, a 25% EDC diet simultaneously administered i.p. ADNF-9 (ALC/ADNF-9), or a pair-fed (PF) liquid diet. At E13, fetal brains were collected from 5 dams from each group, weighed, and frozen for LC-MS/MS procedure. Other fetal brains were fixed for TUNEL staining.


RESULTS
Administration of ADNF-9 prevented alcohol-induced reduction in fetal brain weight and alcohol-induced increases in cell death. Moreover, individual fetal brains were analyzed by LC-MS/MS. Statistical differences in the amounts of proteins between the ALC and ALC/ADNF-9 groups resulted in a distinct data-clustering. Significant upregulation of several important proteins involved in brain development were found in the ALC/ADNF-9 group as compared to the ALC group.


CONCLUSIONS
These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA. youssef.sari@utoledo.edu
Youssef
Y
Sari
Zaneer M
ZM
Segu
Ahmed
A
YoussefAgha
Jonathan A
JA
Karty
Dragan
D
Isailovic
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000002:abnormalities / Q000187:drug effects*; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000008:administration & dosage*; D009479:Neuropeptides / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009842:Oligopeptides; D011247:Pregnancy
D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; D000431:Ethanol