Basic study for risk assessment of embryonic brain development by antidepressant treatment during pregnancy
| Project/Area Number |
18K09271
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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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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Saitama Medical University |
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Principal Investigator |
Sato Tomomi 埼玉医科大学, 医学部, 非常勤講師 (50373311)
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| Co-Investigator(Kenkyū-buntansha) |
梶原 健 埼玉医科大学, 医学部, 教授 (80286103)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | SSRI / 5-HT / セロトニントランスポーター / 脳発生 / 自閉症 / ゼブラフィッシュ / 抗うつ薬 / 胎盤 / 胎児脳発生 / 妊娠 |
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| Outline of Final Research Achievements |
Using zebrafish embryos as a model of human fetuses, we attempted to elucidate effects of antidepressant SSRI and the mechanisms of action on early development of the brain. Serotonin transporter SERT, the target protein of SSRI, was expressed in neural stem/progenitor cells, and localized in the surface of the ventricular zone. Knockdown of SERT facilitated mitoses, suppressed neurogenesis, and exhibited small brains in the embryos. SSRI showed effects similar to SERT knockdown, and those effects reproduced by 5-HT. Our data implied that serotonin was more generated by the maternal placenta than the embryonic brain. In addition, we showed that treatment with serotonin at higher concentrations caused severe growth retardation of the embryos.
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| Academic Significance and Societal Importance of the Research Achievements |
妊娠中の抗うつ薬SSRI服用が出生児の自閉症リスクを高めるとの報告がある。自閉症は、遺伝要因に依存した多因子性疾患であるだけでなく、胎児期の環境要因にも依存する神経発達障害である。セロトニントランスポーターSERTは、自閉症の原因遺伝子の一つであるが、脳の発生過程におけるSSRIの作用とSERTの役割、自閉症発症の分子機構は未だ不明である。セロトニンの進化的起源は古く、脳の発生機構は基本的に保存されていることから、本研究の成果は、SSRIの胎児脳発生に対する副作用の分子機構解明に有用であり、自閉症のリスク評価に必要不可欠なバイオマーカーを探索・同定するための研究基盤となることが期待される。
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Report
(5 results)
Research Products
(6 results)
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[Journal Article] Cereblon Control of Zebrafish Brain Size by Regulation of Neural Stem Cell Proliferation2019
Author(s)
Hideki Ando, Tomomi Sato, Takumi Ito, Junichi Yamamoto, Satoshi Sakamoto, Nobuhiro Nitta, Tomoko Asatsuma-Okumura, Nobuyuki Shimizu, Ryota Mizushima, Ichio Aoki, Takeshi Imai, Yuki Yamaguchi, Arnold J Berk, and Hiroshi Handa
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Journal Title
iScience
Volume: 15
Pages: 95-108
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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