Pathophysiological analysis of endoplasmic reticulum stress for therapy of neurodevelopmental disorders

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18879
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: Kawada Koichi 千葉科学大学, 薬学部, 講師 (30581631)
• Research Collaborator: MIMORI SEISUKE ; TAKEUCHI YUTO
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 自閉スペクトラム症 / 小胞体ストレス / シナプスオーガナイザー

Outline of Final Research Achievements

Neurodevelopmental disorders, which contain autism spectrum disorder (ASD), are dysfunction in central nerve system. In present, the pathogenic mechanism of ASD is related with synaptic organizer, but the detail is unclear. The stresses in gestation induce ASD-like symptoms by having bad influence in embryonic brain. In this study, I investigated the effects induced by ER stress in neural circuit formation. Moreover, I examined the effects of the drug against ER stress on the therapy for neurodevelopmental disorders.
I found that ER stress suppressed expansion of neuronal dendrites. Similarly, the expansion of the dendrites was suppressed in the cerebral cortex of ASD model mice. Moreover, ER stress was decreased in the expression of synaptic organizers in neuronal cell line. Additionally, molecular chaperone 4-phenylbutylic acid (4-PBA) improved the abnormality of social interaction in ASD model mice. Therefore, the relationship is obvious for ER stress and the onset of ASD.

Free Research Field

神経精神薬理学