Feng Mei-Jiang, Yan Shu-E, Yan Qing-Shan
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA.
Brain Res. 2005 May 3;1042(2):125-32. doi: 10.1016/j.brainres.2005.02.017.
Prenatal alcohol exposure produces many developmental defects in the central nervous system. The underlying molecular mechanism, however, has not been fully understood. The present study was undertaken to examine the effects of prenatal alcohol exposure on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in offspring. The pregnant Sprague-Dawley rats received 1 or 3 g/kg of alcohol or an isocaloric solution by intragastric intubation once a day from gestational day (GD) 5 to GD 20. On postnatal day 7-8, pups were killed and the hippocampus, striatum, cortex, and cerebellum dissected out. Levels of BDNF mRNA and proteins, total TrkB proteins and receptor phosphorylation were measured. The results showed that prenatal alcohol exposure at the dose of 1 g/kg/day did not significantly affect BDNF protein levels in any region examined. However, administration of alcohol at the dose of 3 g/kg/day markedly reduced levels of BDNF protein and mRNA in the cortex and hippocampus of offspring. Western blotting showed that prenatal alcohol exposure at the dose of 3 g/kg/day also inhibited TrkB phosphorylation in the hippocampus although no changes in total TrkB protein levels were observed in any region examined. Our data suggest that prenatal alcohol exposure alters both presynaptic and postsynaptic BDNF function in certain brain areas of offspring. These alterations in BDNF function may contribute to the development of alcohol-related birth defects.
孕期酒精暴露会导致中枢神经系统出现多种发育缺陷。然而，其潜在的分子机制尚未完全明确。本研究旨在探讨孕期酒精暴露对后代脑源性神经营养因子（BDNF）及其受体酪氨酸激酶B（TrkB）的影响。将怀孕的Sprague-Dawley大鼠从妊娠第5天（GD）至第20天每天经胃管给予1或3 g/kg酒精或等热量溶液。在出生后第7 - 8天，处死幼崽并取出海马体、纹状体、皮质和小脑。检测BDNF mRNA和蛋白水平、总TrkB蛋白水平及受体磷酸化水平。结果显示，每天1 g/kg剂量的孕期酒精暴露对所检测的任何区域的BDNF蛋白水平均无显著影响。然而，每天3 g/kg剂量的酒精给药显著降低了后代皮质和海马体中BDNF蛋白和mRNA的水平。蛋白质印迹法显示，每天3 g/kg剂量的孕期酒精暴露也抑制了海马体中TrkB的磷酸化，尽管在所检测的任何区域总TrkB蛋白水平均未观察到变化。我们的数据表明，孕期酒精暴露会改变后代某些脑区中突触前和突触后BDNF的功能。BDNF功能的这些改变可能导致与酒精相关的出生缺陷的发生。
