Neurochemical disturbance in a mouse model of Down syndrome

本研究旨在探讨唐氏综合征(DS)小鼠脑内神经递质水平的变化，为DS患者脑内神经化学紊乱提供依据。用高效液相色谱法对DS小鼠模型Ts1Cje脑内各种神经递质及其代谢物的含量进行了定量，结果表明Ts1Cje脑内对多巴胺和5-羟色胺的分解代谢增强。甲基苯丙胺治疗可使Ts1Cje脑内代谢紊乱恢复正常。此外，免疫组织化学分析发现，Ts1Cje的脑中儿茶酚-O-甲基转移酶(COMT)的表达高于野生型。这些发现对阐明DS的病理生理机制具有重要意义，COMT有望成为治疗DS脑异常的新靶点。

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.