Analysis of behavioral quantity by the loss of function of CIN85 related to receptor endocytosis

2008 Fiscal Year Final Research Report

• Project/Area Number: 18590216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Gunma University
• Principal Investigator: SHIMOKAWA Noriaki Gunma University, 大学院・医学系研究科, 准教授 (90235680)
• Co-Investigator(Kenkyū-buntansha): KOIBUCHI Noriyuki 群馬大学, 大学院・医学系研究科, 教授 (80234681)
• Project Period (FY): 2006 – 2008
• Keywords: CIN85 / ドーパミン受容体 / 多動性 / エンドサイトーシス / ノックアウトマウス

Research Abstract

CIN85ノックアウト(KO)マウスの「多動」の原因としてドーパミン及びその受容体の量的、質的変化に焦点をあてて解析した。電気化学検出器(本科研費にて購入)を備えた高速液体クロマトグラフィーでKOマウスの線条体ドーパミン含量を測定した結果、KOマウスでは野生型に比べて線条体ドーパミン含量が170%高値であった。さらに線条体初代培養細胞においてドーパミン刺激後、膜表面に存在するドーパミン受容体は野生型由来で約25%、KOマウスでは70%であった。このエンドサイトーシスの異常がドーパミン刺激の過剰を招き「多動」を誘発している原因の一つと考えられる。本研究から「多動」という行動異常の原因の一つが受容体の膜輸送を司る複合体の分子欠損によることが明らかになった。これは受容体によるシグナルの調節が受容体単一ではなく、多様な膜蛋白質の複合体形成によってもたらされている事を示している点で意義ある成果と考えられる。

Research Products

• [Journal Article] Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism (2009)
  • Author(s): Sajdel-Sulkowska EM, Xu M, Koibuchi N
  • Journal Title: Cerebellum (in press)
  • Peer Reviewed
• [Journal Article] Augmentation of estrogen receptor-mediated transcription by steroid and xenobiotic receptor (2008)
  • Author(s): Rokutanda N, Iwasaki T, Odawara H, Nagaoka R, Miyazaki W, Takeshita A, Koibuchi Y, Horiguchi J, Shimokawa N, Iino Y, Morishita Y, Koibuchi N
  • Journal Title: Endocrine (in press)
  • Peer Reviewed
• [Journal Article] Identification of the functional domain of thyroid hormone receptor responsible for polychlorinated biphenyl-mediated suppression of its action in vitro (2008)
  • Author(s): Miyazaki W, Iwasaki T, Takeshita ATohyama C, Koibuchi N
  • Journal Title: Environ Health Perspect 116 Pages: 1231-1236
  • Peer Reviewed
• [Journal Article] Abnormalities of vertebral formation and Hox expression in congenital kyphoscoliotic rat (2008)
  • Author(s): Seki T, Shimokawa N, Iizuka H, Takagishi K, Koibuchi N
  • Journal Title: Mol. Cell. Bioche 312 Pages: 193-199
  • Peer Reviewed
• [Journal Article] The role of thyroid hormone in developing cerebellum (2008)
  • Author(s): Koibuchi N, Qiu CH, Miyazaki W, Iwasaki T, Shimokawa N
  • Journal Title: Cerebellum 7 Pages: 499-500
  • Peer Reviewed
• [Journal Article] Ahmadiani A. Low-dose morphine induces hyperalgesia through activation of Gas, protein kinase C and L-type Ca^2+ channels in rats (2008)
  • Author(s): Mahani SE, Shimokawa N, Javan M, Maghsodi N, Motamedi F, Koibuchi N
  • Journal Title: J. Neurosci. Res 86 Pages: 471-479
  • Peer Reviewed
• [Journal Article] RORa mutation in Staggerer mouse induces alteration of mRNA levels of neurotrophin family in developing cerebellum (2007)
  • Author(s): Qiu CH, Shimokawa N, Iwasaki T, Parhar IS, Koibuchi N
  • Journal Title: Endocrinology 148 Pages: 1745-1753
  • Peer Reviewed
• [Journal Article] Low dose hydroxylated PCB induces c-Jun expression in PC12 cells (2006)
  • Author(s): Shimokawa N, Miyazaki W, Iwasaki T, Koibuchi N
  • Journal Title: Neurotoxicology 27 Pages: 176-183
  • Peer Reviewed
• [Journal Article] The adrenal gland is a source of stress-induced circulating IL-18 (2006)
  • Author(s): Sugama S, Wang N, Shimokawa N, Koibuchi NFujita M, Hashimoto M, Dhabhar FS, Conti B
  • Journal Title: J. Neuroimmunol 172 Pages: 59-65
  • Peer Reviewed
• [Journal Article] Tamoxifen activates CYP3A4 and MDR-1 genes though steroid and xenobiotic receptor in breast cancer cells (2006)
  • Author(s): Nagaoka R, Iwasaki T, Rokutanda N, Takeshita A, Koibuchi Y, Horiguchi J, Shimokawa N, Iino Y, Morishita Y, Koibuchi N
  • Journal Title: Endocrine 30 Pages: 261-268
  • Peer Reviewed
• [Presentation] Crosstalk between thyroid hormone receptor and retinoid receptor-related orphan receptor (ROR) aand its modulation bypolychlorinated biphenyl (2006)
  • Author(s): Koibuchi N., Qiu C.H., Miyazaki W., Shimokawa N., Iwasaki T.
  • Organizer: 36th Annual Meeting, Society for Neuroscience
  • Place of Presentation: Atlanta, GA, USA
  • Year and Date: 20061014-18
• [Book] 生殖機能In : 集中講義「生理学」(岡田隆夫編) (2008)
  • Author(s): 下川哲昭
  • Total Pages: 276-289
  • Publisher: メジカルビュー社
• [Book] 内分泌生理症例問題他In症例問題から学ぶ生理学(鯉淵典之編)丸善 (2006)
  • Author(s): 鯉淵典之
  • Total Pages: 369