Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
J Biomed Sci. 2011 Oct 21;18(1):77. doi: 10.1186/1423-0127-18-77.
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).
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.
活性依赖性神经营养因子（ADNF-9）的衍生肽已被证明在胎儿酒精暴露模型中具有神经保护作用。我们使用 TUNEL 染色研究了 ADNF-9 对酒精诱导的凋亡的神经保护作用。我们进一步使用液相色谱与串联质谱（LC-MS/MS）研究了 ADNF-9 对抗早期胎儿大脑发育中乙醇致畸作用的蛋白质组结构。
从胚胎第 7 天到 13 天（E7-E13），将 C57BL/6 孕鼠暴露于 25%乙醇衍生的热量[25%EDC，酒精（ALC）]饮食中，同时腹腔内给予 ADNF-9（ALC/ADNF-9）或配对喂养（PF）液体饮食。在 E13 时，从每组 5 只母鼠中收集胎脑，称重并冷冻进行 LC-MS/MS 程序。其他胎脑用于 TUNEL 染色。
ADNF-9 的给药可预防酒精引起的胎脑重量减少和酒精引起的细胞死亡增加。此外，通过 LC-MS/MS 对单个胎脑进行了分析。ALC 和 ALC/ADNF-9 组之间蛋白质数量的统计学差异导致数据聚类明显。与 ALC 组相比，ALC/ADNF-9 组中发现了几种与大脑发育有关的重要蛋白质的显著上调。
这些发现为 ADNF-9 在胎儿酒精暴露模型中的神经保护作用的潜在机制提供了信息。
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