2009 Fiscal Year Final Research Report

Neurochemical disturbance in a mouse model of Down syndrome

Research Project

Project/Area Number	20790089
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Biological pharmacy
Research Institution	The Institute of Physical and Chemical Research
Principal Investigator	ISHIHARA Keiichi The Institute of Physical and Chemical Research, 薬学部, 助教 (80340446)
Project Period (FY)	2008 – 2009
Keywords	ダウン症候群 / 神経伝達物質
Research Abstract	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.