Study of novel physiological function by the system with oxytocin and its receptor.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23380055
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Tohoku University
• Principal Investigator: NISHIMORI Katsuhiko 東北大学, (連合)農学研究科(研究院), 教授 (10164609)
• Co-Investigator(Renkei-kenkyūsha): HIGASHIDA Haruhiho 金沢大学, 医学系, 教授 (30093066) ; ONAKA Tatushi 自治医科大学, 医学部, 准教授 (90177254) ; SAKAMOTO Hirotaka 岡山大学, 自然科学研究科, 教授 (20363971) ; KURODA Kumi 独立行政法人理化学研究所, 脳科学総合研究センター, 研究ユニット長 (90391945) ; YAO Hiromu 東北大学, 生命科学研究科, 教授 (00144353)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 情報伝達 / オキシトシン受容体 / オキシトシン / 社会行動 / 自閉症スペクトラム / 母性行動 / 扁桃体内側核 / セロトニン

Research Abstract

Central oxytocin and its receptor Oxtr have a regulatory function to control social behaviors in mammals, including human. Also, application of oxytocin to Autism patients have been started and reports describing positive cure effects have been accumulated. In this study, we analyzed the mechanism controlling social behaviors by neurons expressing Oxtr in brain First, by crossing fx-type Oxtr KO mice with ePet-Cre mice, we generated mice having 5-HT neurons-specific deletion of Oxtr genes. This line didn't show any impairment in their social memory. In contrast, rescue experiment was carried out by injection of AAV-Cre viral vector to mice brains to induce MeA-specific deletion of Oxtr gene, and it revealed that Oxtr expressing in MeA were essential for social memory. In addition, we found that the glutamatergic neurons expressing Oxtr in rRPa regulated body temperature. We forwarded study of type I taste cells expressing Oxtr, and obtained novel characteristics of these populations.

Research Products

• [Journal Article] Role of oxytocin receptors in modulation of fear by social memory (2014)
  • Author(s): Guzmán,Y.F,, Tronson,N.C., Jovasevic,V., Sato,K., Ivana Mesic, Guedea,A.L., Nishimori,K. and Radulovic,J
  • Journal Title: Psychopharmacology Volume: 231 Pages: 2097-2105
  • DOI: 10.1007/s00213-013-3356-6
  • Peer Reviewed
• [Journal Article] Oxytocin Receptor in the Hypothalamus Is Sufficient to Rescue Normal Thermoregulatory Function in Male Oxytocin Receptor Knockout Mice (2013)
  • Author(s): Ksahara Y, Sato K, Takayanagi Y, Mizukami H, Ozawa K, Hidema S, So K-H, Kawada T, Inoue N, Ikeda I, Roh S-G, Itoi K, and Nishimori K
  • Journal Title: Endocrinology Volume: 154 Pages: 4305-4315
  • DOI: 10.1210/en.2012-2206
  • Peer Reviewed
• [Journal Article] Fear-enhancing effects of septal oxytocin receptors (2013)
  • Author(s): Guzmán,Y.F,, Tronson,N.C., Jovasevic,V., Sato,K., Guedea,A.L., Mizukami,H., Nishimori,K. and Radulovic,J.
  • Journal Title: Nat Neurosci Volume: 16 Pages: 1185-1187
  • DOI: 10.1038/nn.3465
  • Peer Reviewed
• [Journal Article] Mice heterozygous for the oxytocin receptor gene (Oxtr(+/-)) show impaired social behaviour but not increased aggression or cognitive inflexibility : evidence of a selective haploinsufficiency gene effect (2013)
  • Author(s): Sala,M., Braida,D., Donzelli,A., Martucci,R., Busnelli,M., Bulgheroni,E., Rubino,T., Parolaro,D., Nishimori,K. and Chini,B
  • Journal Title: Journal of Neuroendocrino- logy Volume: 25 Pages: 107-118
  • DOI: 10.1111/j.1365-2826.2012.02385.x
  • Peer Reviewed
• [Journal Article] Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton (2012)
  • Author(s): Colaianni G, Sun L, Benedetto A Di, Tamma R, Zhu LL, Cao J, Grano M, Yuen T, Colucci S, Cuscito C, Mancini M, Li J, Nishimori K, Bab I, Lee HJ, Iqbal J, Young WS, Rosen C, Zallone A, and Zaidi M
  • Journal Title: J Biol Chem Volume: 287 Pages: 29159-67
  • DOI: 10.1074/jbc.M112.365049
  • Peer Reviewed
• [Journal Article] Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling (2011)
  • Author(s): de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H
  • Journal Title: Nature Volume: 476 Pages: 293-297
  • DOI: 10.1038/nature10337
  • Peer Reviewed
• [Journal Article] Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice : Aneurobehavioral model of autism (2011)
  • Author(s): Sala,M., Braida,D., Lentini,D., Busnelli,M., Bulgheroni,E., Capurro,V., Finardi,A., Donzelli,A., Pattini,L., Rubino,T., Parolaro,D., Nishimori,K., Parenti,M., and Chini,B
  • Journal Title: Biol Psychiatry Volume: 69 Pages: 875-82
  • DOI: 10.1016/j.biopsych.2010.12.022
  • Peer Reviewed
• [Presentation] 『マウス扁桃体オキシトシン受容体発現ニューロンと社会記憶』"Social Memory and Neurons Expressing Oxytocin Receptor in Medial Amygdala" (2013)
  • Author(s): 西森克彦, 千葉裕太朗 , 佐藤佳亮, 水上浩明 , 日出間志寿
  • Organizer: 第36回日本神経科学大会Neuro2013
  • Place of Presentation: 京都
  • Year and Date: 2013-06-20
• [Presentation] マウスモデルによる中枢性オキシトシン受容体系の社会行動制御メカニズム (2012)
  • Author(s): 西森克彦, 他
  • Organizer: 社会行動と脳ーイメージングと分子ー
  • Place of Presentation: 京都市
  • Year and Date: 2012-02-02
• [Presentation] Oxytocin receptorexpressing neurons and social behaviors : studies with a genetically engineered animal model (2011)
  • Author(s): K Nishimori
  • Organizer: Workshop on Prosocial Behavior
  • Place of Presentation: アトランタ, アメリカ
  • Year and Date: 2011-10-23
• [Presentation] オキシトシン系ペプチドの多様な生理作用と生物多様性 (2011)
  • Author(s): 西森克彦
  • Organizer: 情動研究会
  • Place of Presentation: 岡崎市
  • Year and Date: 2011-10-06
• [Presentation] 生理活性ペプチドの構造・機能と生物多様性 (2011)
  • Author(s): 西森克彦
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-21
• [Presentation] 中枢性オキシトシン受容体の社会行動制御に於ける役割 : 遺伝子KOマウスとOxtr-Venusノックインマウスから判った事 (2011)
  • Author(s): 西森克彦
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜市
  • Year and Date: 2011-09-14
• [Book] 不快な社会刺激は外側中隔のオキシトシン受容体を介し恐怖記憶を強化する 実験医学 (2014)
  • Author(s): 西森克彦,Yomayra F,Guzman, Jelena Radulovic
  • Total Pages: 438-441
• [Remarks]
  • URL: http://www.biochem.tohoku.ac.jp/bunsi/Index-j.html
• [Patent(Industrial Property Rights)] 遺伝子組み換え非ヒト動物 (2013)
  • Inventor(s): 西森克彦, 日出間志寿
  • Industrial Property Rights Holder: 西森克彦, 日出間志寿
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2013-229315
  • Filing Date: 2013-11-05