Centro Riferimento Alcologico Regione Lazio, Universita di Roma La Sapienza, Roma, Italy.
Neurobiol Aging. 2012 Feb;33(2):359-67. doi: 10.1016/j.neurobiolaging.2010.03.005. Epub 2010 Apr 10.
Prenatal ethanol exposure produces severe changes in brain, liver, and kidney through mechanisms involving growth factors. These molecules regulate survival, differentiation, maintenance, and connectivity of brain, liver, and kidney cells. Despite the abundant available data on the short and mid-lasting effects of ethanol intoxication, only few data show the long-lasting damage induced by early ethanol administration. The aim of this study was to investigate changes in nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in brain areas, liver, and kidney of 18-mo-old male mice exposed perinatally to ethanol at 11% vol or to red wine at the same ethanol concentration. The authors found that ethanol per se elevated NGF, BDNF, HGF, and VEGF measured by ELISA in brain limbic system areas. In the liver, early exposure to ethanol solution and red wine depleted BDNF and VEGF concentrations. In the kidney, red wine exposure only decreased VEGF. In conclusion, the present study shows that, in aged mice, early administration of ethanol solution induced long-lasting damage at growth factor levels in frontal cortex, hippocampus, and liver but not in kidney. Otherwise, in mice exposed to red wine, significant changes were observed in the liver and kidney but not in the hippocampus and frontal cortex. The brain differences in ethanol-induced toxicity when ethanol is administered alone or in red wine may be related to compounds with antioxidant properties present in the red wine.
产前乙醇暴露通过涉及生长因子的机制导致大脑、肝脏和肾脏发生严重变化。这些分子调节大脑、肝脏和肾脏细胞的存活、分化、维持和连接。尽管有大量关于乙醇中毒的短期和中期影响的数据,但只有很少的数据显示早期乙醇给药引起的长期损害。本研究旨在研究神经生长因子 (NGF)、脑源性神经营养因子 (BDNF)、肝细胞生长因子 (HGF) 和血管内皮生长因子 (VEGF) 在 18 个月大的雄性小鼠大脑区域、肝脏和肾脏中的变化,这些小鼠在围产期暴露于 11%vol 的乙醇或相同乙醇浓度的红酒中。作者发现,乙醇本身通过 ELISA 在大脑边缘系统区域升高了 NGF、BDNF、HGF 和 VEGF。在肝脏中,早期暴露于乙醇溶液和红酒会耗尽 BDNF 和 VEGF 浓度。在肾脏中,红酒暴露仅降低了 VEGF。总之,本研究表明,在老年小鼠中,早期给予乙醇溶液会导致额叶皮质、海马体和肝脏中生长因子水平的长期损害,但不会导致肾脏损害。另一方面,在暴露于红酒的小鼠中,在肝脏和肾脏中观察到明显变化,但在海马体和额叶皮质中未观察到明显变化。当乙醇单独或在红酒中给予时,大脑中乙醇诱导的毒性差异可能与红酒中具有抗氧化特性的化合物有关。