Molecular mechanisms and enhanced inflammtion in retardation of brain development and cognitive impairment in a mouse model of Down synrome

2016 Fiscal Year Final Research Report

• Project/Area Number: 25460077
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Ishihara Keiichi 京都薬科大学, 薬学部, 講師 (80340446)
• Co-Investigator(Renkei-kenkyūsha): KANAI SHIHO 京都薬科大学, 薬学部, 助手 (40582630)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: ダウン症 / マウスモデル / オミクス解析 / 炎症 / 神経伝達物質

Outline of Final Research Achievements

To elucidate the pathomechanisms underling intellectual disability and developmental delay of the brain in Down syndrome (DS), we employed three "-omics" analyses. Our proteomics and transcriptomics analysis revealed the perturbated expressions of five proteins, which suggest a disturbance of GABAergic interneurogenesis, and increased expressions of inflammation-related genes in the embryonic brain of a mouse model for DS. In addition, our quantitative analysis for neurotransmitters suggest an increased flux through central dopamine and serotonin metabolism in the adult brain of a DS model mouse. Finally, we succeeded to identify the responsible gene for increased expression of inflammation-related gene in the embryonic brain of a DS model mouse. We assume our findings are important to display the developmental delay and intellectual disability in the individuals with DS.

Free Research Field

医歯薬学