Diabetes-induced disturbances in energy and lipid metabolism in the brain

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Ryo 東京大学, 医学部附属病院, 講師 (20396732)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / 脳 / SCAP / 認知機能 / アストロサイト / ステロール

Outline of Final Research Achievements

Diabetes mellitus increases risk for various CNS disorders including cognitive impairment. We focused on alterations in sterol metabolism in the brain. In diabetic mouse brains, cholesterol biosynthesis is reduced due to insufficient insulin action, accompanied by down-regulation of a sterol-sensor molecule SCAP. We found that haploinsufficiency of Scap gene in the whole brain caused impaired cognitive function. AMPK activation, mimicking a diabetic state in the brain, reduced SCAP in astroglial cells. Furthermore, induction of SCAP deficiency in astrocytes provoked disturbances in long-term memory and social cognition.

Free Research Field

糖尿病学