Neurochemical disturbance in a mouse model of Down syndrome

唐氏综合症小鼠模型的神经化学紊乱

• 批准号: 20790089
• 负责人: ISHIHARA Keiichi
• 金额: $ 2.75万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790089/
• 关键词: ダウン症候群; 神経伝達物質; マウスモデル; モデルマウス

The present study was designed to evaluate at the levels of neurotransmitters in the mouse brain with Down syndrome (DS) that could provide evidence for neurochemical disturbance in the brain of DS patient. Quantification for the contents of various neurotransmitters and their metabolites in the brain of Ts1Cje, a mouse model of DS using HPLC analysis revealed that catabolisms for dopamine and serotonin were enhanced in the Ts1Cje brain. The disturbed catabolisms in Ts1Cje brain were normalized by methamphetamine treatment. Additionally, high expression of catechol-O-methyltransferase (COMT) was detected in the Ts1Cje brain compared to that in wild-type littermates on an immunohistochemical analysis. These findings would be important for clarification of DS pathophysiology, and COMT is expected as a new therapeutic target for the anomalies of DS brain.

本研究旨在评估小鼠大脑中唐氏综合症（DS）的神经递质水平，这些水平可以为DS患者大脑的神经化学障碍提供证据。对TS1CJE大脑中各种神经递质及其代谢产物的含量的定量，使用HPLC分析的DS小鼠模型表明，TS1CJE脑中多巴胺和5-羟色胺的分解代谢增强了。通过甲基苯丙胺治疗将TS1CJE脑中扰动的分解代谢归一化。此外，与在免疫组织化学分析中，在TS1CJE脑中检测到Catechol-O-O-甲基转移酶（COMT）的高表达相比，在TS1CJE脑中被检测到。这些发现对于澄清DS病理生理学将很重要，并且预计COMT是DS脑异常的新治疗靶点。

项目成果

Increased lipid peroxidation in Down syndrome mouse models

唐氏综合症小鼠模型中脂质过氧化增加

• 发表时间: 2009
• 期刊: Journal of Neurochemistry VOL.110
• 作者: Keiichi Ishihara;Kenji Amano;Eiichi Takaki;Abdul S. Ebrahim;Atsushi Shimohata;Noriko Shibazaki;Ikuyo Inoue;Mayuko Takaki;Yuto Ueda;Haruhiko Sago;Charles J. Epstein;Kazuhiro Yamakawa;Keiichi Ishihara
• 通讯作者: Keiichi Ishihara

Enlarged Brain Ventricles and Impaired Neurogenesis in the Ts1Cje and Ts2Cje Mouse Models of Down Syndrome

• DOI: 10.1093/cercor/bhp176
• 发表时间: 2010-05-01
• 期刊: CEREBRAL CORTEX
• 影响因子: 3.7
• 作者: Ishihara, Keiichi;Amano, Kenji;Yamakawa, Kazuhiro
• 通讯作者: Yamakawa, Kazuhiro

ダウン症記憶障害の治療のための新しい候補ターゲットシグナル!?(ハイライトポスター)

治疗唐氏综合症记忆障碍的新候选目标信号！？（亮点海报）

• 发表时间: 2010
• 作者: Keiichi Ishihara;Kenji Amano;Eiichi Takaki;Abdul S. Ebrahim;Atsushi Shimohata;Noriko Shibazaki;Ikuyo Inoue;Mayuko Takaki;Yuto Ueda;Haruhiko Sago;Charles J. Epstein;Kazuhiro Yamakawa;Keiichi Ishihara;石原慶一;石原慶一
• 通讯作者: 石原慶一