The neurobehavioral study of the attention-deficit/hyperactivity disorder (ADHD) model rats with abnormal morphogenesis of the hippocampus or the cerebellum

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

• 批准号: 13610088
• 负责人: SUGIOKA Kozo
• 金额: $ 2.56万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13610088/
• 关键词: attention-deficit; hyperactivity disorder; methylazoxymethanol; spontaneous activity; shuttle-box avoidance learning; radial maze learning; water-maze learning; hippocampus; cerebellum; 空間認知障害; 注意欠陥多動障害; 活動性; 神経行動奇形学; 自発運動量; 放射線状迷路学習

We examined the correlation of the behavioral disorders with the morphogenetical abnormality of the brain in the attention-deficit/hyperactivity disorder (ADHD) model animals which were induced by methylazoxymethanol (MAM) injection on the prenatal 15-day (MAM-15 group) or 19-day (MAM-19 group).Behaviorally, 1) the MAM-15 rat showed a hyperactive tendency and the MAM-19 rat showed a hypoactive tendency during dark phase in a home-cage compared with the control rats, although no statistical difference among the groups was found in the open-field activity, during weaning, juvenile and adult periods, 2) the MAM-15 rat showed a facilitated avoidance and the MAM-19 rat showed a retarded avoidance in the shuttle-box avoidance learning situation during adulthood, but not during juvenile period, 3) the MAM-15 rat showed a severe impaired spatial cognition in the radial-maze and the Morris-type water maze learning situations, although the MAM-19 rat showed a moderate deficit, during each developmental stage. The behavioral disorder obtained 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 obtained in the MAM-19 rat correlated with a disorder in foliation of the anterior cerebellum, which were histologically observed in these groups. Our behavioral and histological results suggest that the ADHD-like behavioral disorder may be derived from the hippocampal dysfunction induced by abnormal morphogenesis of the hippocampus.

本研究采用甲基偶氮甲醇（MAM）诱导的注意缺陷多动障碍（ADHD）动物模型，在出生后15 d内观察其行为异常与脑形态发生学异常的关系（MAM-15组）或19天（MAM-19组）在行为学上，1）与对照组大鼠相比，MAM-15大鼠在笼内黑暗期表现出多动倾向，MAM-19大鼠表现出少动倾向，尽管在断奶期、幼年期和成年期的旷场活动中没有发现组间的统计学差异，2）MAM-15大鼠在成年期的梭箱回避学习情境中表现出易化回避，而MAM-19大鼠表现出延迟回避，但在幼年期没有，（3）MAM-15大鼠在径向迷宫和Morris型水迷宫学习中表现出严重的空间认知障碍，而MAM-19大鼠在各个发育阶段表现出中度的空间认知障碍。在MAM-15大鼠中获得的行为障碍与海马的形态学异常（CA 1锥体层和异位神经元团的破坏）相关，并且在MAM-19大鼠中获得的行为障碍与小脑前部的叶形成障碍相关，这在这些组中进行了组织学观察。我们的行为学和组织学研究结果表明，ADHD样行为障碍可能是由海马形态发生异常引起的海马功能障碍引起的。

项目成果

杉岡 幸三(分担): "心理学総合事典(II部心の生物学的基礎 第4章脳の神経情報)"朝倉書店(未定). (2005)

Kozo Sugioka（撰稿人）：《心理学综合百科全书（第二部分：心灵的生物学基础，第 4 章：大脑中的神经信息）》朝仓书店（待定）。

Fukui, Y.: "Comments from the behavioral teratology committee of the Japanese teratology society on OECD guideline for the testing of chemicals, proposal for a new guideline 426, developmental neurotoxicity study"Congenital Anomalies. (未定). (2004)

Fukui, Y.：“日本畸胎学协会行为畸胎学委员会对 OECD 化学物质测试指南的评论，关于新指南 426 的建议，发育性神经毒性研究”先天性异常（TBD）（2004 年）。

Sugioka, K.: "The correlation of spatial cognition impairments with the morphological abnormalities of the CA1 hippocampus in microencephalic rats induced by prenatal・・・"Congenital Anomalies. 41・3. 264-265 (2001)

Sugioka, K.：“产前引起的小脑大鼠的空间认知障碍与 CA1 海马形态异常的相关性……”先天性异常 41・3 (2001)。

Sugioka, K.: "Spatial memory impairment in rats with experimentally-induced disorders in morphogenesis of the hippocampus or anterior cerebellum"Neuroscience Research. Suppl 25 (in press).

Sugioka, K.：“实验诱发海马或小脑前部形态发生障碍的大鼠的空间记忆障碍”神经科学研究。

Hashimoto, M.: "Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats"Journal of Neurochemistry. 81. 1084-1091 (2002)

Hashimoto, M.：“二十二碳六烯酸可防止阿尔茨海默病模型大鼠的学习能力受损”《神经化学杂志》。