Remodeling of the postsynaptic density during postnatal development

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K14830
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kobe University (2020-2021); Institute of Physical and Chemical Research (2018-2019)
• Principal Investigator: Kaizuka Takeshi 神戸大学, 医学研究科, 特命助教 (40782032)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: PSD / シナプス後肥厚 / シナプス / プロテオミクス / 自閉症 / 自閉スペクトラム症

Outline of Final Research Achievements

I analyzed protein composition of the postsynaptic density (PSD) by proteome analysis. During postnatal development, protein involved in synaptic plasticity is found to be significantly increased or decreased in PSD in mouse brain. This is accompanied with altered signal transduction. Correlations with the transcriptome datasets suggested that the increase or decrease in protein levels after 2-week-old mouse is caused by changes in gene expression that occur after postnatal day 4. Similar protein increases and decreases were suggested to occur around birth in primates. Analysis of transcriptome dataset of the patient with autism spectrum disorders suggested that the composition of PSD is more immature in patient brain. I also found that alteration of PSD composition in common marmoset brain after 2-month-old is distinct from that found in postnatal mouse brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、生後発達期のシナプスのタンパク質組成の変化を網羅的に明らかにし、それがどのような意義を持っているか、またどのようなメカニズムにより生じていると考えられるかを示した。これらの結果は、シナプスの成熟を「タンパク質組成」の観点からとらえる考え方を提供したとも言える。また、自閉症などの神経発達障害にもシナプスのタンパク質組成の異常（成熟不全）が関与している可能性を示した。社会的には、自閉症の治療戦略への考え方を提供したという点でも意義があるのではないかと考えている。