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A neurobehavioral study of the attention-deficit/hyperactivity disorder (ADHD) model rat with an abnormal morphogenesis of the hippocampus or the cerebellum using

使用海马或小脑形态发生异常的注意力缺陷/多动障碍 (ADHD) 模型大鼠的神经行为研究

基本信息

批准号：
16530470
负责人：
SUGIOKA Kozo
金额：
$ 2.37万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

We examined the correlation of the behavioral disorders with the morphogenetical abnormality of the brain in the attention-deficit/hyperactivity disorder (AD/HD) model animals which were induced by methylazoxymethanol (MAM) injection on the prenatal 15-day (MAM-15 group) or 19-day (MAM-19 group). Behavioral results were following, 1) the MAM-15 rat showed a hyperactive tendency and the MAM-19 rat showed a hypoactive tendency, which were measured by infra-red sensor during dark phase in a home-cage, during both weaning and adult periods, 2) the MAM-15 rat showed a retardation of the habituation to the environmental visual stimulus changing, and 3) the MAM-15 rat showed a severe impaired spatial cognition (especially spatial working-memory deficit) in the radial-maze and the Morris-type water maze learning situations, although the MAM-19 rat showed a moderate deficit, during both developmental stages. The behavioral disorder observed in the MAM-15 rat correlated with a morphological abnormality of the hippocampus (disruption of the CA1 pyramidal layer and ectopic neuron mass), and the behavioral disorder, although which were moderate, observed in the MAM-19 rat correlated with an abnormal foliation of the anterior cerebellum. Our behavioral and histological results suggest that the AD/HD-like behavioral disorder obtained in the present study may be derived from the brain dysfunction induced by abnormal morphogenesis of the hippocampus.

本研究采用甲基偶氮氧甲醇（MAM-15组）和甲基偶氮氧甲醇（MAM-19组）分别于出生后15 d和19 d建立注意缺陷多动障碍（AD/HD）动物模型，观察其行为障碍与脑形态发生异常的关系。行为学研究结果表明：1）MAM-15大鼠表现出多动倾向，MAM-19大鼠表现出少动倾向，这是在家庭笼中的黑暗阶段，在断奶和成年阶段，通过红外传感器测量的。2）MAM-15大鼠表现出对环境视觉刺激变化的适应延迟，和3）MAM-15大鼠在径向迷宫和莫里斯型水迷宫学习情况下表现出严重的空间认知受损（尤其是空间工作记忆缺陷），尽管MAM-19大鼠在这两个发育阶段表现出中度缺陷。在MAM-15大鼠中观察到的行为障碍与海马的形态异常（CA 1锥体层和异位神经元块的破坏）相关，在MAM-19大鼠中观察到的行为障碍（尽管为中度）与小脑前部的异常叶状结构相关。我们的行为学和组织学结果表明，AD/HD样行为障碍，在本研究中获得的可能来源于海马的异常形态发生诱导的脑功能障碍。