Molecular pathophysiology of neurodevelopmental disorders associated with mutations in the genes encoding voltage-gated sodium channels

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nippon Medical School (2015); The Institute of Physical and Chemical Research (2013-2014)
• Principal Investigator: OGIWARA Ikuo 日本医科大学, 医学部, 准教授 (30373286)
• Research Collaborator: MAZAKI Emi 理化学研究所, 脳科学総合研究センター, 技術員
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: トランスレーショナルリサーチ / 知的障害 / てんかん / 自閉症スペクトラム障害 / ナトリウムチャネル遺伝子

Outline of Final Research Achievements

De novo mutations of the SCN2A encoding a voltage-gated sodium channel Nav1.2 have been associated with epileptic encephalopathy, autism spectrum disorder and intellectual disability. We here found that, in mouse brain, SCN2A was expressed in excitatory neurons and subsets of inhibitory neurons. We also found that mice with a conditional SCN2A deletion in excitatory neurons and those in inhibitory neurons showed normal threshold for seizures induced by chemoconvulsant. We furthermore found that SCN2A knockout mice had deficits in spatial learning and memory, showed enhanced consolidation and decreased extinction of fear-related memory.

Free Research Field

神経科学