Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol

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.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.These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.Fetal alcohol exposure (FAE) or fetal alcohol syndrome (FAS) is a significant worldwide problem. Clinical studies demonstrate that brain growth deficits and neurological disorders are one of the pathological features of FAS or FAE [[1-4]; for review see Ref. [5]]. Experimental studies demonstrated that prenatal alcohol exposure induces brain growth restriction, microcephaly, facial dysmorphology, and abnormal behaviors [6-10].Studies performed in our laboratory reveal that prenatal alcohol exposure induces brain growth deficits at different embryonic stages [for review see Ref. [11]]. The effects of prenatal alcohol exposure might be associated with an apoptotic mechanism [12]. This apoptotic mechanism involves intrinsic mitochondrial and extrinsic pathways such as receptor systems [13,14]. We have recently shown that prenatal alcohol exposure induced apoptosis that might be associated with activation of caspase-3, increases of cytosolic cytochrome c, and decreases of mitochondrial