Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill CB# 7178, Chapel Hill, NC 27599-7178, USA.
Alcohol. 2012 Sep;46(6):603-12. doi: 10.1016/j.alcohol.2012.01.003. Epub 2012 May 7.
Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5 g/kg, s.c., 2 h apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduced MRI total brain volume (4%) with multiple brain regions being reduced in both males and females. Immunohistochemistry indicated reduced frontal cortical parvalbumin immunoreactive (PV + IR) interneurons (18-33%) and reduced Cux1+IR layer II pyramidal neurons (15%) in both sexes. Interestingly, markers of adult hippocampal neurogenesis differed between sexes, with only ethanol treated males showing increased doublecortin and Ki67 expression (52 and 57% respectively) in the dentate gyrus, consistent with increased neurogenesis compared to controls. These findings suggest that P7 ethanol treatment causes persistent reductions in adult brain volume and frontal cortical neurons in both males and females. Increased adult neurogenesis in males, but not females, is consistent with differential adaptive responses to P7 ethanol toxicity between the sexes. One day of ethanol exposure, e.g. P7, causes persistent adult brain dysmorphology.
在出生后第 7 天（P7）给予乙醇处理会导致大量脑细胞死亡，是一种模拟妊娠晚期酒精暴露的模型（Ikonomidou 等人，2000）。为了研究 P7 乙醇处理对成年大脑的长期影响，将小鼠分为两组，分别在 P7 时接受生理盐水或乙醇处理（2.5 g/kg，皮下，2 小时间隔），并在成年（P82）时评估脑体积（使用死后 MRI）和细胞结构（使用免疫组织化学）。接受 P7 乙醇处理的成年小鼠的 MRI 总脑体积减少了 4%，且雄性和雌性小鼠的多个脑区体积均减少。免疫组织化学显示，前额皮质的 parvalbumin 免疫反应性（PV + IR）中间神经元减少了 18-33%，Cux1+IR 层 II 锥体神经元减少了 15%，在雌雄两性中均如此。有趣的是，成年海马神经发生的标志物在两性之间存在差异，只有接受乙醇处理的雄性小鼠在齿状回中出现了双倍皮质酮和 Ki67 表达的增加（分别增加了 52%和 57%），与对照相比，神经发生增加。这些发现表明，P7 乙醇处理会导致成年雄性和雌性小鼠的大脑体积和前额皮质神经元持续减少。雄性小鼠而非雌性小鼠的成年神经发生增加，与两性之间对 P7 乙醇毒性的适应性反应不同有关。仅一天的乙醇暴露（例如 P7）会导致成年大脑形态异常持续存在。
