Analysis of the effect on fetus, by single and continuous administration of oxytocin to pregnant mother prairie vole.

• Project/Area Number: 16K15698
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: Nishimori Katsuhiko 東北大学, 農学研究科, 教授 (10164609)
• Co-Investigator(Kenkyū-buntansha): 竹田 省 順天堂大学, 医学部, 特任教授 (20143456)
• Research Collaborator: HIDEMA Shizu ; YADA Saori ; HIRAYAMA Takashi
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 誘発分娩 / 自閉症スペクトラム障害 / 平原ハタネズミ / CRISPR/Cas9 / 浸透圧ポンプ / ペア形成行動 / オキシトシン / オキシトシン受容体 / 自閉症 / Prairie Vole

Outline of Final Research Achievements

Oxytocin (OXT) is neuromodulator controlling social and prosocial behaviors in animals, and expected as a new drug curing patients of Autistic Spectrum Disorders (ASD). Impaired social behaviors are also known as a core symptom of ASD patients. On the other hand, OXT has been widely used as labor-inducing drug in the area of gynecology. However, recent epidemiological studies reported that exposure of fetus to exogenously administrated OXT might be a risk factor to induce ASD. We studied the effect of exogenously administrated OXT on fetus, and it might induce brain ischemia during induced labor led to cell death in several nuclei, which were implicated as impaired nuclei in mental disorders, however we haven’t found any abnormal social behavior with pups after birth. We continuously need to assess the safety of administrated OXT on pups until their adulthood.

Research Products

• [Int'l Joint Research] Yerkes Natl Prim Res Ctr, Emory U./Pennsylvania St.Univ.(米国)
• [Journal Article] Melanin concentrating hormone modulates oxytocin-mediated marble burying. (2018)
  • Author(s): Nayna, M., Sanathara, N.M., Garau, C., Alachkar, A., Wang, L., Wang, Z., Nishimori, K., Xu, X. and Civelli, O.
  • Journal Title: J.Neuropharmacology Volume: 128 Pages: 22-32
  • DOI: 10.1016/j.neuropharm.2017.09.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Oxytocin Signaling in the Lateral Septum Prevents Social Fear during Lactation. (2018)
  • Author(s): Menon, R., Grund, T., Zoicas, I., Althammer, F., Fiedler, D., Biermeier, V., Bosch, O. J., Hiraoka, Y., Nishimori, K., Eliava, M., Grinevich, V., & Neumann I. D.
  • Journal Title: Current Biology Volume: 28 Issue: 7 Pages: 1066-1078.e6
  • DOI: 10.1016/j.cub.2018.02.044
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice (2017)
  • Author(s): Okabe, S., Tsuneoka, Y., Takahashi, A., Ooyama, R., Watarai, A., Maeda, S., Honda, Y., Nagasawa, M., Mogi, K., Nishimori, K., Kuroda, M., Koide, T., Kikusui, T.
  • Journal Title: Psychoneuroendocrinology Volume: 79 Pages: 20-30
  • DOI: 10.1016/j.psyneuen.2017.01.036
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons (2017)
  • Author(s): in, Y.-T., Chen, C.-C., Huang, C.-C., Nishimori, K., & Hsu, K.-S.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1-16
  • DOI: 10.1038/s41467-017-00675-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice (2017)
  • Author(s): Nasanbuyan Naranbat、Yoshida Masahide、Takayanagi Yuki、Inutsuka Ayumu、Nishimori Katsuhiko、Yamanaka Akihiro、Onaka Tatsushi
  • Journal Title: Endocrinology Volume: 159 Issue: 2 Pages: 763-775
  • DOI: 10.1210/en.2017-00606
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] MeAのOxtrシグナルはVPA投与マウスのASD様行動を改善する。 (2017)
  • Author(s): 木野崎萌、堀合眞知、宮崎慎至、矢田紗織、日出間志寿、西森克彦
  • Organizer: 第40回日本神経科学大会
• [Presentation] オキシトシンによる共感性行動の神経制御機構解析 -平原ハタネズミとマウスの比較解析- (2017)
  • Author(s): 矢田紗織、堀江謙吾、西森克彦
  • Organizer: 第40回日本神経科学大会
• [Presentation] 自閉症モデルマウスにおけるOxt作用機構の解析 (2017)
  • Author(s): 堀合眞知、木野崎萌、矢田紗織、日出間志寿、西森克彦
  • Organizer: 第40回日本神経科学大会
• [Presentation] オキシトシンが制御する共感性の神経回路の解明 (2017)
  • Author(s): 矢田紗織、堀江謙吾、日出間志寿、西森克彦
  • Organizer: 日本動物行動関連学会・研究会合同大会（行動2017）
• [Presentation] Generation of Oxtr gene modified prairie voles by CRISPR/Cas to understand the neural mechanisms of social attachment in mammals. (2017)
  • Author(s): Kengo Horie, Saori Yada, Saki Adachi, Shingo Suzuki, Takashi Hirayama, Tomokazu Fukuda, Shizu Hidema, Katsuhiko Nishimori
  • Organizer: 第9回光操作研究会
• [Presentation] Analysis of empathic neural circuit regulated by oxytocin. (2017)
  • Author(s): 矢田紗織、堀江謙吾、日出間志寿、西森克彦
  • Organizer: 第9回光操作研究会
• [Presentation] Prenatal minocycline treatment alters synaptic protein expression, in oxytocin receptor-knockout mice. (2017)
  • Author(s): SHINJI MIYAZAKI, SHIZU HIDEMA, KATSUHIKO NISHIMORI
  • Organizer: 北米神経科学会
• [Presentation] Analysis of empathic neural circuit regulated by oxytocin. (2017)
  • Author(s): Saori Yada、Kengo Horie、Shizu Hidema、Katsuhiko Nishimori
  • Organizer: 北米神経科学会
• [Presentation] 閉症スペクトラム障害治療薬の開発に向けたオキシトシン受容体アゴニスト探索 (2016)
  • Author(s): 鈴木紳吾、堀江謙吾、岸貴之、井上飛鳥、矢田紗織、日出間志寿、青木淳賢、西森克彦
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] Generation of oxytocin receptor modified prairie voles by using CRISPR/Cas. (2016)
  • Author(s): K. HORIE, T. HIRAYAMA, S. SUZUKI, T. FUKUDA, S. HIDEMA, K. NISHIMORI
  • Organizer: Neuroscience 2016（北米神経科学会2016年年会）
  • Place of Presentation: San Diego/USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Remarks] 東北大学農学研究科・分子生物学分野
  • URL: http://www.biochem.tohoku.ac.jp//bunsi/index-j.html
• [Remarks] 分子生物学分野
  • URL: http://www.biochem.tohoku.ac.jp//bunsi/index-j.html