Mechanisms and therapeutic strategy for cognitive dysfunction in Angelman syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09611
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hokkaido University
• Principal Investigator: EGAWA Kiyoshi 北海道大学, 医学研究院, 助教 (40450829)
• Research Collaborator: KAWANO Osamu 北海道大学, 医学院, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アンジェルマン症候群 / 自閉症スペクトラム / GABA

Outline of Final Research Achievements

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the UBE3A gene. We have recently shown that tonic form of GABAergic inhibition is significantly decreased in the cerebellar granule cells of Ube3a knockout mice (AS mice). Because tonic inhibition is ubiquitously present within CNS, deregulation of tonic inhibition may be involved in pathophysiology of various in AS. To clarify this, we investigated GABAergic function in the hippocampus and thalamus of AS mice.Tonic inhibition of CA1 hippocampal pyramidal neurons was significantly decreased in AS mice, while thalamic relay neurons not.Thus, deregulation of tonic inhibition in AS mice differs by brain region. THIP, a enhancer of tonic inhibition in the entire brain, did not improve cortical dysfunctions such as epilepsy or memory deficit, suggesting that the discrepancy of intensity of tonic inhibition among brain regions itself may contribute to the pathophysiology of AS.

Free Research Field

小児神経学、細胞神経生理学