Kalev-Zylinska Maggie L, During Matthew J
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, 1142 Auckland, New Zealand.
J Neurosci. 2007 Sep 26;27(39):10456-67. doi: 10.1523/JNEUROSCI.2789-07.2007.
Epidemiological studies have suggested a negative correlation between alcohol intake and Alzheimer's disease. In vitro, ethanol negatively modulates NMDA receptor function. We hypothesized that chronic moderate alcohol intake leads to improved memory via adaptive responses in the expression of NMDA receptors and downstream signaling. We fed liquid diets containing no, moderate, or high amounts of ethanol to control and matched rats with hippocampal knock-down of the NR1 subunit. Rats with increased hippocampal NR1 expression were also generated to determine whether they had a phenotype similar to that of ethanol-fed animals. We found that moderate ethanol intake improved memory, increased NR1 expression, and changed some aspects of neurotrophin signaling. NR1 knock-down prevented ethanol's facilitatory effects, whereas hippocampal NR1 overexpression mimicked the effect of chronic low-dose ethanol intake on memory. In contrast, high-dose ethanol reduced neurogenesis, inhibited NR2B expression, and impaired visual memory. In conclusion, adaptive changes in hippocampal NMDA receptor expression may contribute to the positive effects of ethanol on cognition.
流行病学研究表明，酒精摄入量与阿尔茨海默病之间存在负相关。在体外实验中，乙醇对N-甲基-D-天冬氨酸（NMDA）受体功能具有负向调节作用。我们推测，长期适度饮酒通过NMDA受体表达及下游信号传导的适应性反应，改善记忆力。我们给对照组和海马NR1亚基基因敲除的配对大鼠喂食不含乙醇、适量乙醇或高剂量乙醇的流质饮食。我们还培育出海马NR1表达增加的大鼠，以确定它们是否具有与喂食乙醇的动物相似的表型。我们发现，适度饮酒可改善记忆力、增加NR1表达，并改变神经营养因子信号传导的某些方面。NR1基因敲除可阻止乙醇的促进作用，而海马NR1过表达则模拟了长期低剂量饮酒对记忆力的影响。相反，高剂量乙醇会减少神经发生、抑制NR2B表达并损害视觉记忆。总之，海马NMDA受体表达的适应性变化可能有助于乙醇对认知的积极作用。
