Elucidation of mechanisms regulating impulsivity in the developmental disorders and its pharmacotherapy : From a viewpoint of brain reward system

发育障碍中冲动的调节机制及其药物治疗的阐明：从大脑奖励系统的角度

基本信息

批准号：
21790515
负责人：
YAMAGUCHI Taku
金额：
$ 2.41万
依托单位：
Nagasaki International University (2010-2011)Hokkaido University (2009)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

In this study, to elucidate the mechanisms regulating impulsivity in the developmental disorders, I mainly explored the key neuronal molecules related to the expression/formation of impulsive behaviors in model rats of developmental disorder. I investigated using the juvenile stroke-prone spontaneous hypertensive rat (SHRSP/Ezo: Ezo) as an appropriate animal model of "attention deficit hyperactivity disorder (ADHD)" and we also used juvenile SHRSP/Izm (Izm) and SHRSP/Ngsk (Ngsk) which are similar to genetic background of Ezo in the SHR substrain. In comparison with juvenile WKY/Ezo which is a genetic control for Ezo, impulsive behavior in the elevated plus-maze test only observed in the Ezo, but not Izm and Ngsk, which behavioral properties were specific for Ezo. Base on the behavioral result, I explored the polymorphic regions linked Ezo-specific behavior differ from that of Izm and Ngsk using the database determined by global analysis of single nucleotide polymorphism (SNP). 137 SNPs linked Ezo-specific behavior were identified in the 21,032 candidate genes based on SNPs of Brown Norway rat. These SNPs linked Ezo-specific behavior were retained on the chromosome 7, 9 and X-chromosome. These findings suggested that genetic background associated with impulsive behavior in the Ezo as an ADHD model rat was related to the SNPs on the chromosome 7, 9 and X-chromosome and functional molecules linked to the development and formation of neuronal cells.

在本研究中，为了阐明发育障碍中冲动的调节机制，我主要探讨了发育障碍模型大鼠中与冲动行为表达/形成相关的关键神经元分子。我使用幼年易发生中风的自发性高血压大鼠（SHRSP/Ezo：Ezo）作为“注意力缺陷多动障碍（ADHD）”的合适动物模型进行了研究，我们还使用了幼年SHRSP/Izm（Izm）和SHRSP/Ngsk（Ngsk））与 SHR 亚系中 Ezo 的遗传背景相似。与作为 Ezo 遗传控制的幼年 WKY/Ezo 相比，高架十字迷宫测试中的冲动行为仅在 Ezo 中观察到，而 Izm 和 Ngsk 则没有，而 Izm 和 Ngsk 是 Ezo 特有的行为特性。基于行为结果，我使用通过单核苷酸多态性（SNP）的全局分析确定的数据库探索了与Izm和Ngsk不同的与Ezo特定行为相关的多态性区域。基于挪威棕色大鼠的 SNP，在 21,032 个候选基因中鉴定出 137 个与 Ezo 特异性行为相关的 SNP。这些与 Ezo 特异性行为相关的 SNP 保留在 7、9 号染色体和 X 染色体上。这些发现表明，与 ADHD 模型大鼠 Ezo 冲动行为相关的遗传背景与 7、9 和 X 染色体上的 SNP 以及与神经元细胞发育和形成相关的功能分子有关。