Molecular mechanisms for regression of matured synapses as a neuronal basis for Rett syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19672
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Institute for Physiological Sciences (2017); Tokyo Women's Medical University (2016)
• Principal Investigator: Narushima Madoka 生理学研究所, 基盤神経科学研究領域, 准教授 (30596177)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: シナプス / 発達 / 維持 / mGluR1 / MeCP2 / レット症候群

Outline of Final Research Achievements

Rett syndrome is a neurodevelopmental disorder that is induced by a genetic mutation of the Methyl CPG-binding protein 2 (MeCP2) and that is characteristic for regression of once acquired cognitive functions and behaviors. Regression of matured synaptic connectivity has been reported in the afferent synapses of the visual thalamus in MeCP2-knockout (KO) mice but molecular mechanisms underlying regression of synaptic connectivity in relation with MeCP2 was unclear. We reported that KO mice of the metabotropic glutamate receptor subtype 1 (mGluR1) showed similar phenotype as MeCP2-KO mice that exhibited regression of once matured synaptic connectivity in the visual thalamus. mGluR1 expressed in a similar developmental time course with MeCP2 and was necessary and sufficient for maintenance of matured synaptic connectivity in the thalamic afferent synapses. These results strongly suggest that mGluR1 and MeCP2 have strong relationship in the maintenance of matured neuronal circuits.

Free Research Field

神経科学