The RNA-based mechanism underlying pathophysiology in the neurodevelopmental disorders

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K14355
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokai University
• Principal Investigator: IIJIMA Takatoshi 東海大学, 創造科学技術研究機構, 准教授 (90383702)
• Research Collaborator: SCHEIFFELE Peter Universität Basel, Dept. of Zellbiologie, Biozentrum, Professor ; SCHEIFFELE Peter Universität Basel, Dept. of Biomedicine und Physiologie, Professor
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 自閉症スペクトラム障害 / バルプロ酸 / 抑制性神経細胞 / シナプス

Outline of Final Research Achievements

Autism spectrum disorders (ASDs) are a neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders, but increases the risk of the unborn child to develop an ASD during pregnancy. Therefore, VPA-exposed rodent models may allow for identification of synaptic pathophysiology underlying ASD risk. Here, we systematically probed alterations in synaptic proteins that might contribute to autism-related behavior in the offspring of in utero VPA-exposed mice. Moreover, we tested whether direct VPA exposure of cultured neurons may recapitulate the molecular alterations seen in vivo. VPA-exposed neurons in culture exhibit a significant decrease in the number of GABAergic synapses. This shift in excitatory/inhibitory balance results in increased spontaneous activity. Therefore, our study highlights a mechanism underlying the synaptic pathophysiology in this ASD model.

Free Research Field

神経薬理学