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Neurotrophic factors and cognitive function after alcohol intoxication in mice model

小鼠酒精中毒模型中神经营养因子与认知功能的关系

基本信息

批准号：
22590636
负责人：
JAMAL Mostofa
金额：
$ 3.08万
依托单位：
Kagawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Here we investigated the effects of ethanol (EtOH) and acetaldehyde (AcH) on behavior,and mRNA levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and c-fos at 30 min after EtOH in Aldehyde dehydrogenase 2 knock (Aldh2-KO), Apolipoprotein E knockout (ApoE-KO) and wild type (WT) mice. Eight-arm-radial maze and Morris-water maze showed that 1) 2.0 g/kg EtOH impaired spatial memory in all three strains, while lower doses did not have consistent memory effects, 2) a probe trial(drug-free state) showed a sustained memory impairment in mice that had received 2.0 g/kg EtOH previously, regardless of strain, 3) ApoE-KO mice learned more slowly than WT mice, and the Aldh2-KO mice learned more quickly.Real time PCR showed that 1) EtOH increased c-fos mRNA expression in ALDH2-KO (1 and 2g/kg) and WT (2.0 g/kg), 2) 2.0 g/kg of EtOH decreased ChAT mRNA in Aldh2-KO mice, while acetylcholinesterase mRNA expression was increased in both strains, 3) acute EtOH failed to alter the mRNA levels of NGF and BDNF and 4)Aldh2-KO mice showed a distinctly lower level of ChAT mRNA and a higher level of NGF mRNA versus WT mice. Our observation suggests that high EtOH and AcH can alter cholinergic markers and this effect did not modify the levels of NGF and BDNF.

本研究观察了乙醇（EtOH）和乙醛（AcH）对乙醛脱氢酶2基因敲除（Aldh 2-KO）、载脂蛋白E基因敲除（ApoE-KO）和野生型（WT）小鼠行为以及EtOH后30 min神经生长因子（NGF）、脑源性神经营养因子（BDNF）和c-fos mRNA水平的影响。八臂-放射状迷宫和Morris-水迷宫实验表明：1）2.0 g/kg乙醇对3种品系的空间记忆均有损害，而低剂量乙醇对3种品系的空间记忆无影响; 2）探索实验表明，（无药物状态）在先前接受2.0 g/kg EtOH的小鼠中显示出持续的记忆障碍，而与品系无关，3）ApoE-KO小鼠比WT小鼠学习更慢，真实的时间PCR结果显示：1）乙醇可促进ALDH 2-KO细胞c-fos mRNA的表达（1和2g/kg）和WT（2.0 g/kg），2）2.0 g/kg乙醇降低Aldh 2-KO小鼠ChAT mRNA表达，而两种品系的乙酰胆碱酯酶mRNA表达增加，3）急性EtOH不能改变NGF和BDNF的mRNA水平; 4）与WT小鼠相比，Aldh 2-KO小鼠显示出明显较低的ChAT mRNA水平和较高的NGF mRNA水平。我们的观察表明，高乙醇和乙酰胆碱可以改变胆碱能标记物，这种影响并没有改变神经生长因子和脑源性神经营养因子的水平。