Study on the effect of endocrine disruptor on memory, learning and emotion in mice

内分泌干扰物对小鼠记忆、学习和情绪影响的研究

基本信息

批准号：
12836008
负责人：
ENOMOTO Taira
金额：
$ 2.69万
依托单位：
Faculty of Human Development
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

In order to study the effect of endocrine disrupter on learning, memory and emotion in mice, we have established knockout mouse strain defective to nel12 gene which is expressed mainly in hippocampus in mouse brain. Using this system, we have studied the LTP(Long-term potentiation) and hippocampal dependent memory and learning of normal, and knockout mice in water-maze system. Furthermore, we have studied expression and distribution of carboxypeptidase B in the subregions of the hippocampus of normal and Alzheimer's human brain.Result :1) Nell2 gene knockout mice has revealed normal behavior in water maze compared with normal mice : both normal and knockout mice require 4〜6 trials for learning water maze. On the other hand, the induction of physiological LTP in hippocampus was much higher in knockout mice than normal mice, indicating that LTP system in knockout mice become more sensitive.2) In avoiding learning system, knockout mice have learned to avoid electrical stimulation faster t … More han normal mice. Further, knockout mice have the electrical stimulation in memory longer than normal mice. These results indicate that knockout mice may be potentiated in certain leaning and memory system such as avoiding learning.3) During the study of nel12 gene knockout mice , we have found that the nel12 gene knockout mice are male-specifically defective in fertilization. All knockout female were pregnant in mating with +/+,-/+, -/- male, respectively. On the other hand, all knockout male were defective in fertilization with +/+,-/+, -/- female. These results clearly indicate that knockout of nel12 gene induces male-specific unfertilization.4) In order to study the mechanism of male-specific unfertilization, we have stdudied sperm formation, sperm motility, sperm morphology, and genes related to sperm-egg binding. Sperm in knockout mice was normal in its motility, number and morphology, indicating that sperm formation is normal in knockout mice.5) We have also studied gene expression of sperm-egg binding factors such as fertilin and cyritestin in normal and knockout mice. Both genes were expressed normally in knockout mice testis. Less

为了研究内分泌干扰物对小鼠学习、记忆和情绪的影响，我们建立了主要在小鼠大脑海马区表达的nel12基因缺陷的小鼠品系，并利用该系统对LTP（Long-）进行了研究。术语增强）和水迷宫系统中正常小鼠和基因敲除小鼠的海马依赖性记忆和学习此外，我们还研究了羧肽酶 B 在海马分区中的表达和分布。结果：1）与正常小鼠相比，Nell2基因敲除小鼠在水迷宫中表现出正常行为：正常小鼠和敲除小鼠都需要4〜6次试验才能学习水迷宫。基因敲除小鼠海马的生理LTP远高于正常小鼠，表明基因敲除小鼠的LTP系统变得更加敏感。2）在回避学习系统中，基因敲除小鼠比正常小鼠更快地学会了躲避电刺激。此外，基因敲除小鼠的记忆电刺激时间比正常小鼠长。这些结果表明，基因敲除小鼠在某些学习和记忆系统中可能会增强，例如回避学习。3）在nel12基因敲除小鼠的研究中，我们发现： nel12基因敲除小鼠在受精方面存在雄性特异性缺陷，所有敲除雌性小鼠均在与+/+、-/+、-/-雄性交配时怀孕。与+/+、-/+、-/-雌性受精缺陷。这些结果清楚地表明nel12基因的敲除会导致雄性特异性不受精。4)为了研究雄性特异性不受精的机制，我们对精子进行了研究。基因敲除小鼠的精子活力、数量和形态均正常，表明基因敲除小鼠的精子形成正常。 5）我们还研究了正常和基因敲除小鼠精卵结合因子（如生育素和cyritestin）的基因表达，这两种基因在基因敲除小鼠睾丸中均正常表达。