High ethanol and acetaldehyde impair spatial memory in mouse models: Opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory
High ethanol and acetaldehyde impair spatial memory in mouse models: Opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory
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DOI：
10.1016/j.pbb.2012.02.006
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发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Kinoshita, Hiroshi
中科院分区：
文献类型：
--
作者：
Jamal, Mostofa;Ameno, Kiyoshi;Kinoshita, Hiroshi
乙醛脱氢酶2缺乏可能直接导致过量乙醛（AcH）积累后，乙醇（EtOH）饮用和AcH介导的一些行为影响的EtOH。载脂蛋白E被认为与注意力和记忆力的改变有关。我们选择了Aldh 2基因敲除（Aldh 2-KO），ApoE基因敲除，和他们的野生型（WT）对照小鼠检查乙醇和乙酰胆碱对空间记忆的影响，并比较可能的关系，遗传缺陷和记忆使用两种行为评估。小鼠训练4天，在第4天腹膜内给予EtOH（0.5、1.0、2.0 g/kg）。在第5天在Morris水迷宫（MWM）中在非EtOH状态下进行探针试验。结果表明，2.0 g/kg EtOH增加了错误，表明所有研究小鼠在八臂径向迷宫（RAM）上的记忆障碍。1克/千克EtOH损害Aldh 2-KO和ApoE-KO小鼠的表现，但不损害WT小鼠的表现。我们发现EtOH对MWM性能的影响相似，2.0 g/kg EtOH增加了乳酸。1克/千克EtOH增加Aldh 2-KO和WT小鼠的乳酸，但不增加ApoE-KO小鼠的乳酸。Aldh 2-KO小鼠中2.0 g/kg EtOH诱导的记忆障碍更大，表明AcH效应。此外，在先前接受2.0 g/kg EtOH的小鼠中，用于探针试验的时间较短。ApoE-KO小鼠学习更慢，而Aldh 2-KO小鼠学习更快。RAM和MWM的结果都表明，高EtOH和AcH损害小鼠的空间记忆，而较低的剂量没有一致的记忆效果。此外，我们得出结论，遗传差异可能是乙醇对记忆的一些影响的基础。(C)2012 Elsevier Inc. All rights reserved.
Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory. (C) 2012 Elsevier Inc. All rights reserved.