Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats.
Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats.
复制标题
急性乙醇暴露对幼年大鼠海马和小脑 GAP-43 和 BDNF 表达的相反影响。
DOI：
10.1016/j.alcohol.2010.12.004
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Perrone-Bizzozero,NI
中科院分区：
文献类型：
--
作者：
Kulkarny,VV;Wiest,NE;Marquez,CP;Nixon,SC;Valenzuela,CF;Perrone-Bizzozero,NI
青少年的大脑特别容易受到酒精的影响，在这个发育年龄的中毒往往会产生长期的影响。本研究探讨了单次急性乙醇暴露对青春期大鼠小脑和海马神经元生长相关蛋白-43（GAP-43）和脑源性神经营养因子（BDNF）基因表达的影响。将出生后第23天（P23）的雄性Sprague-Dawley大鼠暴露于乙醇蒸汽2 h，2 h恢复期后，收获小脑和海马，并取样用于血液酒精浓度（BAC）测定。我们发现，这种暴露导致平均BAC为174 mg/dL，这与人类青少年在狂饮后的水平相似。分别通过定量逆转录PCR和蛋白质印迹法对总RNA和蛋白质进行分析，结果表明，单次乙醇暴露显著降低了小脑中GAP-43 mRNA和蛋白质的水平，但增加了海马中mRNA和蛋白质的水平。BDNF mRNA和蛋白质水平也增加，在海马，但不是在这些动物的小脑。原位杂交结果显示，GAP-43和BDNF的mRNA水平增加，主要是由酒精暴露在海马齿状回颗粒细胞和CA 3神经元。总体而言，报告的可塑性相关基因GAP-43和BDNF在幼年大鼠中的表达变化与酗酒对运动协调和认知功能的已知有害影响一致。
The adolescent brain is particularly vulnerable to the effects of alcohol, with intoxications at this developmental age often producing long-lasting effects. The present study addresses the effects of a single acute ethanol exposure on growth-associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) gene expression in neurons in the cerebellum and hippocampus of adolescent rats. Male postnatal day 23 (P23) Sprague–Dawley rats were exposed to ethanol vapors for 2h and after a recovery period of 2h, the cerebellum and hippocampus were harvested and samples were taken for blood alcohol concentration (BAC) determinations. We found that this exposure resulted in a mean BAC of 174mg/dL, which resembles levels in human adolescents after binge drinking. Analyses of total RNA and protein by quantitative reverse transcription PCR and western blotting, respectively, revealed that this single ethanol exposure significantly decreased the levels of GAP-43 mRNA and protein in the cerebellum but increased the levels of mRNA and protein in the hippocampus. BDNF mRNA and protein levels were also increased in the hippocampus but not in the cerebellum of these animals. In situ hybridizations revealed that GAP-43 and BDNF mRNA levels were primarily increased by alcohol exposure in hippocampal dentate granule cells and CA3 neurons. Overall, the reported alterations in the expression of the plasticity-associated genes GAP-43 and BDNF in juvenile rats are consistent with the known deleterious effects of binge drinking on motor coordination and cognitive function.