ペプチドニューロンによる神経回路機能修飾の分子・細胞メカニズム

• Project/Area Number: 20021012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: 岡 良隆 The University of Tokyo, 大学院・理学系研究科, 教授 (70143360)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥6,700,000 (Direct Cost: ¥6,700,000); Fiscal Year 2009: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2008: ¥3,400,000 (Direct Cost: ¥3,400,000)
• Keywords: 神経科学 / 生理学 / 脳・神経 / 神経修飾 / 生理活性 / ペプチド / GnRH / キスペプチン / 動物

Research Abstract

メダカにおいて、既に報告した遺伝子kiss1のほかに、そのパラログとみなしうる遺伝子kiss2を発見したので、両者の生殖中枢制御機能について解析した。まず各種脊椎動物のゲノムデータベースを検索し、系統発生的な考察を加えたところ、脊椎動物進化の初期にすでに2種類のキスペプチンが存在したことが明らかとなった。魚類でもミドリフグなどではゲノム中にkiss1が見出されず、kiss2のみが確認された。そこで、kiss2が生殖調節に関与している可能性についてkiss1と比較しつつ解析した。in situ hybridization法により繁殖・非繁殖状態でmRNA量を解析したところ、両者は異なる神経細胞集団に存在しており、kiss1は繁殖状態で発現が高く非繁殖状態で低いのに対してkiss2の発現には有意な変動は検出されなかった。また、メスのkiss1遺伝子発現は卵巣除去により強く抑制を受けるがkiss2遺伝子発現は全く影響を受けなかった。さらに、kiss1ニューロンはエストロゲン受容体α(ERα)を発現するが、kiss2ニューロンは発現しないことが分かった。これらのことから、メダカではkiss1のみが性ステロイドに感受性をもち生殖調節に関与しているがkiss2は生殖以外の新たな機能を進化の途上で獲得したのではないか、と結論付けられた。
一方で、3種類全てのGnRHニューロンについて、それぞれがGFP標識されたトランスジェニックメダカを用いて電気生理学的解析を行ったところ、下垂体刺激ホルモンとしてはたらくGnRH1ニューロンと脳内で神経修飾作用をもつGnRH2, GnRH3ニューロンでは電気活動パターンが異なることがわかった。

Research Products

• [Journal Article] Regular pacemaker activity characterizes GnRH 2 neurons recorded from GFP-transgenic medaka (2010)
  • Author(s): Kanda, S., Nishikawa, K., Karigo, T., Okubo, K., Isomae, S, Abe, H., Kobayashi, D., Oka, Y.
  • Journal Title: Endocrinology 151 Pages: 695-701
  • Peer Reviewed
• [Journal Article] Hypothalamic kiss1 but not kiss2 neurons are involved in estrogen feedback in medaka(Oryzias latipes) (2010)
  • Author(s): Mitani, Y., Kanda, S., Akazome, Y., Zempo, B., Oka, Y.
  • Journal Title: Endocrinology 151 Pages: 1751-1759
  • Peer Reviewed
• [Journal Article] Excitatory action of GABA in the terminal nerve gonadotropin-releasing hormone neurons (2010)
  • Author(s): Nakane, R., Oka, Y.
  • Journal Title: Journal of Neurophysiology 103 Pages: 1375-1384
  • Peer Reviewed
• [Journal Article] Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain (2010)
  • Author(s): Akazome, Y., Kanda, S., Okubo, K., Oka, Y.
  • Journal Title: Journal of Fish Biology, Special Issue "Reproductive Physiology' 76 Pages: 161-182
  • Peer Reviewed
• [Journal Article] Primary culture of the isolated terminal nerve-gonadotrophin releasing hormone(GnRH)neurones derived from adult teleost(dwarf gourami, Colisa lalia)brain for the study of peptide release mechanisms (2009)
  • Author(s): Abe, H., Oka, Y.
  • Journal Title: Journal of Neuroendocrinology 21 Pages: 489-505
  • Peer Reviewed
• [Journal Article] Possible role of oestrogen in pubertal increase of Kissl/Kisspeptin expression in discrete hypothalamic areas of female rats (2009)
  • Author(s): Takase, K., Uenoyama, Y., Inoue, N., Matsui, H., Yamada, S., Shimizu, M., Homma, T., Tomikawa, J., Kanda, S., Matsumoto, H., Oka, Y., Tsukamura, H., Maeda, K.-I.
  • Journal Title: Journal of Neuroendocrinology 21 Pages: 527-537
  • Peer Reviewed
• [Journal Article] Three types of gonadotrophin-releasing hormone neurones and steroid-sensitive sexually dimorphic kisspeptin neurones in teleosts (2009)
  • Author(s): Oka, Y.
  • Journal Title: Journal of Neuroendocrinology 21 Pages: 334-338
  • Peer Reviewed
• [Journal Article] Primary culture of the isolated terminal nerve-gonadotrophin releasing hormone(GnRH)neurones derived from adult teleost(dwarf gourami, Colisa Jolla)brain forthe study of peptide release mechanisms (2009)
  • Author(s): Abe, H., and Oka, Y.
  • Journal Title: Journal of Neuroendocrinology 21 Pages: 489-505
  • Peer Reviewed
• [Journal Article] Possible role of oestrogen in pubertal increase of Kiss1/Kisspeptin expression in discrete hypothalamic areas of femalerats (2009)
  • Author(s): Takase, K., Uenoyama, Y., Inoue, N., Matsui, H. Yamada, S., Shimizu, M. Homma, T., Tomikawa, J., Kanda, S., Matsumoto, H., Oka, Y., Tsukamura, H., and Maeda, K.-I.
  • Journal Title: Journal of Neuroendocrinology (in press)
  • Peer Reviewed
• [Journal Article] Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually-dimorphic kisspeptin neurons in medaka(Oryzias latipes) (2008)
  • Author(s): Kanda, S., Akazome, Y., Yamamoto, N., Yamada, S., Tsukamura, H., Maeda, K., and Oka, Y.
  • Journal Title: Endocrinology 149 Pages: 2467-2476
  • Peer Reviewed
• [Journal Article] Coordinated synchronization in the electrically coupled network of terminal nerve gonadotropin-releasing hormone neurons as demonstrated by double patch-clamp study (2008)
  • Author(s): Haneda, K., and Oka, Y.
  • Journal Title: Endocrinology 149 Pages: 3540-3548
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of GnRH-like peptide in the brain of the cephalopod spear squid, Loligo bleekeri (2008)
  • Author(s): Amano, M., Oka, Y., Nagai, Y., Amiya, N., and Yamamori, K.
  • Journal Title: General and ComparatiVe Endocrinology 156 Pages: 277-284
  • Peer Reviewed
• [Journal Article] Identification and expression analysis of peroxisome proliferator-activated receptors cDNA in a reptile, the leopard gecko(Eublepharis macularius) (2008)
  • Author(s): Kato, K., Oka, Y., and Park, M.K.
  • Journal Title: Zoological Science 25 Pages: 492-502
  • Peer Reviewed
• [Presentation] 単一細胞電気穿孔法を用いて外来遺伝子導入した終神経GnRHニューロンにおける分泌小胞の可視化 (2009)
  • Author(s): 阿部秀樹、入江高行、岡良隆
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] キンギョ嗅球神経回路におけるGnRHペプチドの神経修飾作用 (2009)
  • Author(s): 河合喬文、阿部秀樹、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] メダカにおける視床下部 GnRHニューロン活動と下垂体遺伝子発現の日内変動 (2009)
  • Author(s): 苅郷友美、神田真司、相川雅人、阿部秀樹、大久保範聡、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] メダカ脳における kiss1および kiss2ニューロンの生殖制御に対する関与 (2009)
  • Author(s): 三谷優太、赤染康久、神田真司、善方文太郎、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] メダカキスペプチン神経系による視索前野GnRH神経系の制御 (2009)
  • Author(s): 神田真司、赤染康久、大久保範聡、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] GFPトランスジェニックメダカを用いたGnRH2ニューロンの生理学的解析 (2009)
  • Author(s): 西川圭、神田真司、阿部秀樹、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] メダカGnRH3ニューロンにおける co-transmitter としてのグルタミン酸 (2009)
  • Author(s): 赤染康久、神田真司、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] 終神経GnRHニューロンのペースメーカー活動に対するGABAの興奮性作用 (2009)
  • Author(s): 中根亮、岡良隆
  • Organizer: 日本動物学会第80回大会
  • Place of Presentation: 静岡
• [Presentation] Kisspeptin neurons act closely but indirectly on GnRH 1 neuronsvia local interneurons but not on GnRH 2 or 3 neurons in medaka (2009)
  • Author(s): Kanda, S., Akazome, Y., Okubo, K., Okamura, H., Oka, Y.
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience 2009
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] Diurnal regulation of GnRH1 neuronal activities and gonadotropin subunit transcription in a daily spawning fish, medaka (2009)
  • Author(s): 苅郷友美, 神田真司, 相川雅人,阿部秀樹, 大久保範聡, 岡良隆
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience 2009
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] Visualization of peptidergic dense cored vesicles in the terminal nerve(TN)-gonadotropin releasing hormone(GnRH)neurons by single cell electroporation of exogenous genes (2009)
  • Author(s): 阿部秀樹, 入江高行, 岡良隆
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience 2009
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] Electrophysiological, anatomical, and molecular characterization of GnRH neurons in dwarf gourami and GFP transgenic medaka (2009)
  • Author(s): 岡良隆
  • Organizer: The 36th International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
• [Presentation] Electrophysiological and anatomical characterization of three distinct GnRH neuronal populations in the GFP transgenic medaka (2008)
  • Author(s): Kanda, S., Okubo, K., Isomae, S., Abe, H., Kobayashi, D., Takeda, H., Aida, K., Nagahama, Y., and Oka, Y.
  • Organizer: Annual Meeting Society for Neuroscience 2008
  • Place of Presentation: Washington DC, U.S.A
  • Year and Date: 2008-11-17
• [Presentation] Primary culture of the isolated terminal nerve-gonadotropin releasing hormone neurons derived from adult teleost brain and their electrophysiological properties (2008)
  • Author(s): Abe, H., and Oka, Y.
  • Organizer: Annual Meeting Society for Neuroscience 2008
  • Place of Presentation: Washington DC, U.S.A
  • Year and Date: 2008-11-17
• [Presentation] Calcium oscillation of the olfactory non-sensory cells in the goldfish (2008)
  • Author(s): Kawai, T., Abe, H., and Oka, Y.
  • Organizer: Annual Meeting Society for Neuroscience 2008
  • Place of Presentation: Washington DC, U.S.A
  • Year and Date: 2008-11-17
• [Presentation] Coordinated synchronization in the electrically coupled network of terminal nerve GnRH(gonadotropin-releasing hormone) neurons as demonstrated by double patch-clamp study (2008)
  • Author(s): Oka, Y., and Haneda, K.
  • Organizer: Annual Meeting Society for Neuroscience 2008
  • Place of Presentation: Washington DC, U.S.A
  • Year and Date: 2008-11-17
• [Presentation] 脊椎動物に共通する生殖の中枢制御のしくみをメダカの脳から知る (2008)
  • Author(s): 岡良隆
  • Organizer: 第101回日本繁殖生物学会シンポジウム「新規生理活性因子メタスチン」
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-20
• [Presentation] Medaka brain teaches us the mechanisms of the central regulation of reproduction common to the vertebrate species (2008)
  • Author(s): Oka, Y.
  • Organizer: 第35回日本神経内分泌学会・第23回日本下垂体研究会シンポジウム「視床下部・下垂体調節機構の新展開」
  • Place of Presentation: 東京
  • Year and Date: 2008-08-28
• [Presentation] Evolutionary aspects of peptidergic nervous systems in the vertebrate brain (2008)
  • Author(s): Oka, Y.
  • Organizer: International Seminar : Evolutionary Studies in Behavioral Neuroscience
  • Place of Presentation: Yokosuka
• [Presentation] Functional analysis of the physiology of peptidergic systems using the transgenic medaka Neurobiology of,Animal Behavior and Communication (2008)
  • Author(s): Oka, Y.
  • Organizer: 31st Annual meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo
• [Presentation] GABAergic excitation in the terminal nerve GnRH neurons (2008)
  • Author(s): Nakane, R., and Oka, Y.
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] 終神経GnRHニューロンへのFMRFamideペプチドの過分極性作用に関する電気生理学的解析 (2008)
  • Author(s): 齊藤健、阿部秀樹、岡良隆
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Presentation] 単一細胞電気穿孔による終神経GnRHニューロンへの外来分子導入法 (2008)
  • Author(s): 入江高行、尾崎令、阿部秀樹、岡良隆
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Presentation] キンギョ嗅上皮におけるカルシウム振動 (2008)
  • Author(s): 河合喬文、阿部秀樹、岡良隆
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Presentation] メダカ脳内kiss1遺伝子発現は卵巣エストロゲンにより調節され生殖状態を反映する (2008)
  • Author(s): 神田真司、赤染康久、松永拓也、山本直之、山田俊児、東村博子、前多敬一郎、岡良隆
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Presentation] Three types of GnRH neurons and steroid-sensitive sexually dimorphic kisspeptin neurons in teleosts (2008)
  • Author(s): Oka, Y.
  • Organizer: US/Japan Neurosteroid Symposium 2008
  • Place of Presentation: Gifu
• [Presentation] Distribution of kisspeptin neurons in the CNS, with attention also to comparative aspects of Kissl/GPR54 system (2008)
  • Author(s): Vaudry, H., and Oka, Y.
  • Organizer: 1st world conference on kisspeptin signaling in the brain
  • Place of Presentation: Cordoba, Spain
• [Presentation] Primary culture system of fish GnRH neurons for the cellular Physiological studies of effects of kisspeptin (2008)
  • Author(s): Abe, H., and Oka, Y.
  • Organizer: 1st world conference on kisspeptin signaling in the brain
  • Place of Presentation: Cordoba, Spain
• [Presentation] Quantitative expression profiling of kissl and its receptor in the teleost medaka (2008)
  • Author(s): Okubo, K., Kanda, S., and Oka, Y.
  • Organizer: 1st world conference on kisspeptin signaling in the brain
  • Place of Presentation: Cordoba, Spain
• [Presentation] Possible novel form of kisspeptin and kisspeptin receptors in the medaka, Oryzias latipes (2008)
  • Author(s): Akazome, Y., Kanda, S. Mitani, Y., Okubo, K., and Oka, Y.
  • Organizer: 1st world conference on kisspeptin signaling in the brain
  • Place of Presentation: Cordoba, Spain
• [Presentation] Kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medak(Oryzias latipes) (2008)
  • Author(s): Kanda, S., Akazome, Y. Yamamoto, N., Yamada, S. Tsukamura, H., Maeda, K., and Oka, Y.
  • Organizer: 1st world conference on kisspeptin signal ing in the brain
  • Place of Presentation: Cordoba, Spain
• [Remarks]
  • URL: http://www.biol.s.u-tokyo.ac.jp/users/naibunpi/Oka/Oka_lab_publications.html