Brain Mechanism of Aggression

• Project/Area Number: 17330151
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental psychology
• Research Institution: UNIVERSITY of TSUKUBA
• Principal Investigator: OGAWA Sonoko University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究科, 教授 (50396610)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥15,500,000 (Direct Cost: ¥15,500,000); Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000); Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: Aggressive Behavior / Estrogen Receptors / Activity / Emotionality / Social Investigation / Anxiety-Related Behavior / Serotonin

Research Abstract

During the funding period, we have worked to determine the role of estrogen receptor β (ER-β) in the regulation of aggressive behavior in mice in relation to the levels of anxiety levels, social recognition and stress responsiveness.
(1) In the first set of the studies, we tested the effects of estrogen replacement on the levels of anxiety in gonadectomized male mice of ER-b knockout (βERKO) as well as wild-type (WT). The levels of anxiety measured during the light-dark transition tests significantly decreased by estrogen treatment in WT, but not in βERKO, male mice. We also measured the mRNA levels of serotonin transporter (SERT) in ER-β rich midbrain dorsal raphe nuclei. Again, estrogen increased SERT mRNA levels in WT mice but it failed to do so in βERKO mice.
(2) Aggressive behavior of male mice is known to first appear around the time of puberty onset at 5-6weeks of age. In our previous studies, we found an increase of aggression in PERKO mice at the pubertal age suggesting disruption of inhibitory brain system. In the second set of studies, we studied the effects of stress loading on the onset of aggressive behavior around the puberty age. Aggressive behavior measured at 5weeks of age was greatly decreased in mice those separated from their mothers during neonatal period. Decreased levels and a delayed onset of aggression at pubertal age were particularly pronounced in βERKO male mice compared to WT mice. Therefore, we concluded that ER-β might be involved in the development of stress responsiveness around the time of pubertal onset of aggression.

Research Products

• [Journal Article] Silencing of estrogen receptor in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. (2007)
  • Author(s): Musatov, S., Chen, W., Pfaff, D.W., Mobbs, C.V., Yang, X.-J., Clegg, D.J., Kaplitt, M.G., Ogawa, S.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 104 Pages: 2501-2507
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Silencing of estrogen receptor in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. (2007)
  • Author(s): Musatov, S., Chen, W, Pfaff, D.W., Mobbs, C.V., Yang, X.-J., Clegg, D.J., Kaplitt, M.G, Ogawa, S.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 104 Pages: 2501-2507
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Silencing of estrogen receptor in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. (2007)
  • Author(s): Musatov, S., Chen, W., Pfaff, D.W., Mobbs, C.V., Yang, X.-J., Clegg, D.J., Kaplitt, M.G., Ogawa, S
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 104 Pages: 2501-2507
• [Journal Article] Inadvertent social information and the avoidance of parasitized male mice : A role for oxytocin. (2006)
  • Author(s): Kavaliers, M., Choleris, E., Agmo, A., Braun, W.J., Colwell, D.D., Muglia, L.J., Ogawa, S., Pfaff, D.W.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 4293-4298
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Estrogen receptor β gene disruption potentiates estrogen-inducible aggression but not sexual behavior in male mice. (2006)
  • Author(s): Nomura, M., Andersson, S., Korach, K.S., Gustafsson, J-A., Pfaff, D.W., Ogawa, S.
  • Journal Title: European Journal of Neuroscience 23 Pages: 1860-1868
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Knockdown of estrogen receptor α using viral-mediated RNA interference abolishes female sexual behavior. (2006)
  • Author(s): Musatov, S.A., Chen, W., Pfaff, D.W., Kaplitt, M., Ogawa, S.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 10456-10460
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of estrogen receptor α, β, and oxytocin in social discrimination : a detailed behavioral analysis with knockout female mice. (2006)
  • Author(s): Choleris, E., Ogawa, S., Kavaliers, M., Gustafsson, J-A., Korach, K.S., Muglia, L.J., Pfaff, D.W.
  • Journal Title: Genes, Brain and Behavior 5 Pages: 528-539
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor α knockout mice. (2006)
  • Author(s): Tomihara, K., Kaitsuka, T., Soga, T., Korach, K.S., Pfaff, D.W., Takahama, K., Ogawa, S.
  • Journal Title: Neuroreport 17 Pages: 1169-1173
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] From gene networks underlying sex determination and gonadal differentiation to the development of neural networks regulating sociosexual behavior. (2006)
  • Author(s): Crews, D., Lou, W., Fleming, A., Ogawa, S.
  • Journal Title: Brain Research 1126 Pages: 109-121
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Estrogen receptor β gene disruption potentiates estrogen-inducible aggression but not sexual behavior in male mice. (2006)
  • Author(s): Nomura, M., Andersson, S., Korach, KS., Gustafsson, J-A., Pfaff, D.W., Ogawa, S.
  • Journal Title: European Journal of Neuroscience 23 Pages: 1860-1868
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Knockdown of estrogen receptor a using viral-mediated RNA interference abolishes female sexual behavior. (2006)
  • Author(s): Musatov, S.A., Chen, W, Pfaff, D.W., Kaplitt, M., Ogawa, S.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 10456-10460
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of estrogen receptor a, b, and oxytocin in social discrimination : a detailed behavioral analysis with knockout female mice. (2006)
  • Author(s): Choleris, E., Ogawa, S., Kavaliers, M., Gustafsson, J-A., Korach, K.S., Muglia, L.J., Pfaff, D.W.
  • Journal Title: Genes, Brain and Behavior 5 Pages: 528-539
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor a knockout mice. (2006)
  • Author(s): Tomihara, K., Kaitsuka, T, Soga, T., Korach, K.S., Pfaff, D.W., Takahama, K, Ogawa, S.
  • Journal Title: Neuroreport 17 Pages: 1169-1173
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inadvertent social information and the avoidance of parasitized male mice : A role for oxytocin. (2006)
  • Author(s): Kavaliers, M.Cholenris, E.Agmo, A., Braun, W.J.Colwell, D.D., Muglia, L.J., Ogawa, S., Pfaff, D.W.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 4293-4298
• [Journal Article] Involvement of estrogen receptor receptor α,β, and oxytocin in social discrimination : a detailed behavioral analysis with knockout female mice. (2006)
  • Author(s): Choleris, E., Ogawa, S., Kavaliers, M., Gustafsson, J-A., Korach, K.S., Muglia, L.J., Pfaff, D.W.
  • Journal Title: Genes, Brain and Behavior 5 Pages: 528-539
• [Journal Article] Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor a knockout mice. (2006)
  • Author(s): Tomihare, K., Kaitseka, T., Soga, T., Karachi, K.S., Pfaff, D.W., Taka hama, K., Ogawa, S.
  • Journal Title: Neuroreport 17 Pages: 1169-1173
• [Journal Article] Inadvertent social information and the avoidance of parasitized male mice : A role for oxytocin. (2006)
  • Author(s): Kavaliers, M.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 4293-4298
• [Journal Article] Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats. (2005)
  • Author(s): Parhar, I.S., Soga, T., Ogawa, Satoshi, Ogawa, Sonoko, Pfaff, D.W., Sakuma, Y.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 102 Pages: 5880-5885
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats : Effects of adult ovariectomy and estradiol replacement. (2005)
  • Author(s): Cataldo, G., Bernal, S., Markowitz, A., Ogawa, S., Ragnauth, A., Pfaff, D.W., Bodnar, R.J.
  • Journal Title: Brain Research 1059 Pages: 13-19
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of the oxytocin gene in the recognition and avoidance of parasitized males by female mice. (2005)
  • Author(s): Kavaliers, M., Agmo, A., Choleris, E., Muglia, L.J., Ogawa, S., Pfaff, D.W.
  • Journal Title: Animal Behaviour 70 Pages: 693-702
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats : Effects of adult ovariectomy and estradiol replacement. (2005)
  • Author(s): Cataldo, G, Bernal, S., Markowitz, A., Ogawa, S., Ragnauth, A., Pfaff, D.W., Bodnar, RJ.
  • Journal Title: Brain Research 1059 Pages: 13-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of the oxytocin gene in the recognition and avoidance of parasitized males by female mice. (2005)
  • Author(s): Kavaliers, M., Agmo, A., Choleris, E., Muglia, L.J., Ogawa, S., Pfaff, D.W.
  • Journal Title: Animal Behavior 70 Pages: 693-702
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inadvertent social information and the avoidance of parasitized male mice : A role for oxytocin. (2005)
  • Author(s): Kavaliers, M., Choleris, E., Agmo, A., Braun, W.J.Colwell, D.D., Muglia, L.J., Ogawa, S., Pfaff, D.W.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 103 Pages: 4293-4298
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats. (2005)
  • Author(s): Parhar, I.S.
  • Journal Title: Proceedings of the National Academy of Sciences, U.S.A. 102 Pages: 5880-5885
• [Journal Article] Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats : Effects of adult ovariectomy and estradiol replacement. (2005)
  • Author(s): Cataldo, G.
  • Journal Title: Brain Research 1059 Pages: 13-19
• [Journal Article] Involvement of the oxytocin gene in the recognition and avoidance of parasitized males by female mice. (2005)
  • Author(s): Kavaliers, M.
  • Journal Title: Animal Behaviour 70 Pages: 693-702
• [Journal Article] Differential involvement of estrogen receptor α, β, and oxytocin in social discrimination : a detailed behavioral analysis with knockout female mice.
  • Author(s): Choleris, E.
  • Journal Title: Genes, Brain and Behavior in press
• [Journal Article] Estrogen receptor β gene disruption potentiates estrogen-inducible aggression but not sexual behavior in male mice.
  • Author(s): Nomura, M.
  • Journal Title: European Journal of Neuroscience in press
• [Book] Biology of Aggression (2006)
  • Author(s): Ogawa, S., Nomura, M., Choleris, E., Pfaff, D.W.
  • Total Pages: 512
  • Publisher: Oxford University Press
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 脳神経科学イラストレイテッド (2006)
  • Author(s): 小川園子
  • Total Pages: 372
  • Publisher: 羊土社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Brain Sciences, Illustrated (In Japanese) (2006)
  • Author(s): Ogawa, S.
  • Publisher: Yodosha
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 神経科学イラストレイテッド(2^<nd>Ed.) (2006)
  • Author(s): 小川園子
  • Total Pages: 372
  • Publisher: 羊土社
• [Book] Biology of Aggression (2006)
  • Author(s): Ogawa, S.
  • Total Pages: 512
  • Publisher: Oxford University Press
• [Book] Gene Therapy of the Central Nervous System : From Bench to Bedside. (2005)
  • Author(s): Musatov, S.A., Pfaff, D.W., Kaplitt, M., Ogawa, S.
  • Total Pages: 370
  • Publisher: Elsevier
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 生体統御システムと内分泌撹乱 (2005)
  • Author(s): 小川園子
  • Total Pages: 321
  • Publisher: Springer
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Endocrine Disrupters and Biological Regulatory System (In Japanese) (2005)
  • Author(s): Ogawa, S.
  • Publisher: Springer
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Gene Therapy of the Central Nervous System : From Bench to Bedside. (2005)
  • Author(s): Musatov, S.A.
  • Total Pages: 370
  • Publisher: Elsevier