Screening research of new agonist for oxytocin receptor based on scientific evidence based on brain nervous system
| Project/Area Number |
17K07745
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Fukushima Medical University (2019)
Tohoku University (2017-2018) |
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Principal Investigator |
Hidema Shizu 福島県立医科大学, 医学部, 助教 (30241558)
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| Co-Investigator(Kenkyū-buntansha) |
長 由扶子 東北大学, 農学研究科, 助教 (60323086)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | オキシトシン / オキシトシン受容体 / 向社会行動 / 社会行動 / 神経回路 / TGFαshedding assy / TGFα / shedding assay / 自閉症スペクトラム / アデノ随伴ウイルス / TGFα shedding assay / 神経科学 / 食品 |
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| Outline of Final Research Achievements |
In 12000 compounds from three libraries, we searched new agonist for Oxtr, we got two candidates by TGFa shedding assay. Next, we selected one compound by Ca2+ imaging assay for Oxtr, but the activity was weak compared with Oxt. Analysis of the projections from the OXTR+ neurons in the MeA activated by social stimuli revealed projections to the LS, and from the OXTR+ neurons in the LS activated by social stimuli revealed projections to the CA1. On the other hands, Resveratrol which is known to have anti-oxidative activity, through the regulation of Sirt1 expression prevented the abnormal activation of microglia and ameliorated the ASD-like behavior of Oxtr-KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
神経ホルモンオキシトシンとその受容体であるオキシトシン受容体（OXT-OXTR）システムは自閉症、不安障害、うつ病、健忘症の改善効果が報告され、実用化に備えその詳細なメカニズムの解明が急がれている。本研究では社会行動の際に活性化するOXTR発現神経回路の一端を明らかにした。今後はOXTR発現神経細胞の生理的特徴を解析し、臨床応用を目指す。一方で、ブドウや赤ワインに含まれる抗酸化物質レスベラトロールがOXTR遺伝子欠損マウスの示す、社会性異常を改善することを明らかにした。約1200種の化合物からOXT様作用を示す化合物をスクリーニングし候補として1種の低分子を得た。今後、活性の詳細を解析する。
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Report
(4 results)
Research Products
(26 results)
