The synaptic insufficient delivery hypothesis of autism based on PET findings
| Project/Area Number |
16H05373
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | University of Fukui |
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Principal Investigator |
Matsuzaki Hideo 福井大学, 子どものこころの発達研究センター, 教授 (00334970)
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| Co-Investigator(Kenkyū-buntansha) |
謝 敏カク 福井大学, 子どものこころの発達研究センター, 助教 (40444210)
松崎 伸介 和歌山県立医科大学, 医学部, 准教授 (60403193)
片山 泰一 大阪大学, 連合小児発達学研究科, 教授 (80333459)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 自閉症 / セロトニントランスポーター / AMPA型グルタミン酸受容体 / シナプス膜移行 / E/Iバランス / NSF / シナプス / SERT / AMPA受容体 / 児童・青年期精神医学 |
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| Outline of Final Research Achievements |
In this study, we generated and maintained NSF hetero KO mice and NSF conditional KO mice for experiments. As a result, NSF hetero KO mice exhibited autism-like behavior through social interaction, communication and stereotyped behavior. In these mice, SERT / AMPA receptor delivery to the cell membrane in the brain was insufficient. Significant attenuation of LTD amplitude was also confirmed in the mice, which suggests that E / I balance is disturbed in the hippocampus CA1 region of NSF hetero KO mice. Therefore, we concluded that NSF hetero KO mice could be a novel model of autism spectrum disorder and presented at international conferences. On the other hand, NSF conditional KO mice failed to grow up to 6 weeks unfortunately, which inhibited the progress of this study.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた成果は、すでに報告された自閉症のセロトニン動態をよく説明するため、自閉症のメカニズム解明に迫る新たな病態仮説構築の可能性を孕んでいる。次に解決すべき問題は、このシナプス分子膜移行の異常が自閉症の治療標的となるかどうかである。そこでAMPA受容体のシナプス膜移行を促す化合物edonerpic maleateと運動負荷をNSFヘテロKOマウスに与えて、マウスに現れる自閉症様の表現型が修復できるかどうかを検証する計画「シナプス膜移行異常モデルを用いた新規自閉症治療標的の検討」を令和元年度基盤研究Bとして申請し、採択された。この試みが成功すれば、新たな自閉症治療手段の開発につながる。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder.2017
Author(s)
Makinodan M, Iwata K, Ikawa D, Yamashita Y, Yamamuro K, Toritsuka M, Kimoto S, Okumura K, Yamauchi T, Yoshino H, Tsujii M, Sugiyama T, Tsuchiya K, Mori N, Matsuzaki H, Kishimoto T.
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Journal Title
Neurochem Int.
Volume: 104
Pages: 1-5
DOI
Related Report
Peer Reviewed
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[Journal Article] Microglia-derived neuregulin expression in psychiatric disorders.2017
Author(s)
Ikawa D, Makinodan M, Iwata K, Ohgidani M, Kato TA, Yamashita Y, Yamamuro K, Kimoto S, Toritsuka M, Yamauchi T, Fukami SI, Yoshino H, Okumura K, Tanaka T, Wanaka A, Owada Y, Tsujii M, Sugiyama T, Tsuchiya K, Mori N, Hashimoto R, Matsuzaki H, Kanba S, Kishimoto T.
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Journal Title
Brain Behav Immun.
Volume: 61
Pages: 375-385
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Fetal Environment and Glycosylation Status in Neonatal Cord Blood: A Comprehensive Mass Spectrometry-based Glycosylation Analysis.2016
Author(s)
Sato R, Tsuchiya KJ, Matsuzaki H, Takei N, Itoh H, Kanayama N, Suda T, Watanabe H, Ohashi T, Tanaka M, Nishimura S, Maekawa M, HBC study group
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Journal Title
Medicine (Baltimore).
Volume: 95(14)
Issue: 14
Pages: e3219-e3219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Phosphoinositide responsive Phldb2 regulates synaptic plasticity.2016
Author(s)
Xie MJ, Yagi H, Iguchi T, Oka Y, Fukazawa Y, Matsuzaki H, Iwata K, Ishikawa Y, Sato, M.
Organizer
The Society for Neuroscience 46th annual meeting
Place of Presentation
San Diego Convention Center, San Diego, CA 92101, USA
Year and Date
2016-11-13
Related Report
Int'l Joint Research
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