2003 Fiscal Year Annual Research Report

ペプチド神経修飾系の生物機能に関する分子から行動レベルまでの横断的研究

Research Project

Project/Area Number	15370032
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The University of Tokyo
Principal Investigator	岡良隆東京大学, 大学院・理学系研究科, 教授 (70143360)
Co-Investigator(Kenkyū-buntansha)	赤染康久東京大学, 大学院・理学系研究科, 助手 (50302807) 松田学東京大学, 大学院・理学系研究科, 助手 (30282726)
Keywords	ペプチドニューロン / 開口放出 / 神経修飾 / 分子生理学 / カルシウム / イメージング / パッチクランプ / GnRH
Research Abstract	1)GnRH開口放出とイオンチャネル活動・細胞内Ca^<2+>濃度のリアルタイム同時測定従来の岡らの研究成果から,環境の変化は神経伝達物質やホルモンという形で神経系・内分泌系の信号を生成することにより終神経GnRH細胞の細胞膜に存在する伝達物質・ホルモン受容体を活性化し,それと共役する細胞内情報伝達機構によって,終神経GnRH細胞の細胞体および脳内に広く分布する神経突起からのGnRH放出量を調節し,これによって,広範囲の神経系の機能を修飾して動物の神経系が環境の変化に柔軟に適応することを可能にする,と考えられる。このような考えを支持するためには,まず,GnRH放出をリアルタイムに測定しつつ,神経伝達物質やホルモンなどを作用させたときにGnRH放出がどう変化するかを知る必要がある。また,一般に開口放出が起きるには細胞内Ca^<2+>濃度の上昇が必要だが,ペプチドニューロンにおいては細胞内Ca^<2+>濃度の時空間的変化と,SNARE蛋白質などの開口放出分子装置の働きとの関係が未解決である。そこで,まず脳スライスを用いて単一終神経GnRH細胞からパッチ電極で電気活動記録を行い,今年度は膜電位依存性Ca^<2+>チャネルに注目して電気生理学的解析を行った。その結果,GnRHニューロンの持つ膜電位依存性Ca^<2+>チャネルのサブタイプがすべて同定でき,さらに,それらの一部だけが特異的にGnRHペプチドによって修飾を受けることを証明した。 2)GnRH受容体の脳内分布の解析終神経GnRH系が神経修飾作用を行うには必然的に脳内GnRH受容体を介しているはずで,その意味でGnRH受容体の脳内分布を知ることは神経修飾作用の生物機能を調べる上で必須である。我々はすでにDG脳内のGnRH受容体遺伝子のクローニングに着手し,そのアミノ酸配列を解明しつつあるので,この情報を基に,in situ hybridization (ISH)を行ってGnRH受容体の脳内分布を解析した。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Amano, M., Oka, Y., Yamanome, T., Okuzawa, K., Yamamori, K.: "Immunocytochemical localization and ontogenic development melanin-concentrating hormone in the brain of a pleuronectiform fish, the barfin flounder."Cell and Tissue Research. 311. 71-77 (2003)
[Publications] Kiya, t., Oka, Y.: "Glutamate receptors in the terminal nerve gonadotropin-releasing hormone neurons of the dwarf gourami (teleost)."Neuroscience Letters. 345. 113-116 (2003)
[Publications] Amano, M., Okubo, K., Yamanome, T., Oka, Y., Kawaguchi, N., Aida, K., Yamamori, K.: "Ontogenic development of three GnRH systems in the brain of a pleuronectiform fish, brain flounder."Zoological Science. (in press). (2004)
[Publications] Ishizaki, M., Iigo, M., Amano, M., Oka, Y.: "Different modes of gonadotropin-releasing hormone (GnRH) release from multiple GnRH systems as revealed by radioimmunoassay using brain slices of a teleost, the dwarf gourami (Colisa lalia)."Endocrinology. (in press). (2004)
[Publications] Ishikawa, M., Tsutsui, H., Cosson, J., Oka, Y., Morisawa, M.: "Strategies for sperm chemotaxis in the siphonophores and ascidians : a numerical simulation study."Biological Bulletin. (in press). (2004)
[Publications] Kawahara, R., Imaoka, T., Matsuda, M., Mori, T.: "Up-regulation of thymosin beta 4 gene expression in experimentally-induced uterine adenomyosis in mice."In Vivo. 17. 561-565 (2003)
[Publications] Fujiko Masui, Manabu Matsuda, Takao Mori: "Vitamin A prevents the irreversible proliferation of vaginal epithelium induced by neonatal injection of keratinocyte growth factor in mice."Cell Tiss Res. 311. 251-258 (2003)
[Publications] Ryouka Kawahara, Manabu Matsuda, Takao Mori: "Increase in the number of integrinbeta1-immunoreactive monocyte-lineage cells in experimentally-induced adenomyosis in mice."Life Sci. 73. 907-916 (2003)
[Publications] Manabu Matsuda, Jason A.Lockefeer, Nelson D.Horeseman: "Aldolase C/Zebrin gene regulation by prolactin during pregnancy and loctation."Endocrine. 20. 91-100 (2003)
[Publications] Matsuda, M., Imaoka, T., Vomachka, AJ, Gudelsky, GA, Hou, Z., Mistry, M, Bailey, JP, Nieport, KM, Walther, DJ, Bader, M, Horseman, ND: "Serotonin regulates mammary gland development via an autocrine-paracrine loop."Dev Cell. 6. 193-203 (2003)
[Publications] Hazuki Aikawa, Sachiko Koyama, Manabu Matsuda, Keiko Nakahashi, Yasuhisa Akazome, Takao Mori: "Relief effect of vitamin A on the decreased motility of sperm and the increased incidence of malformed sperm in mice exposed neonatally to bisphenol A."Cell Tiss Res. 315. 119-124 (2003)
[Publications] Manabu Matsuda, Fujiko Masui, Takao Mori: "Neonatal estrogenization leads to increased expression of cellular retinol binding protein 2 in the mouse reproductive tract."Cell Tiss Res. (in press). (2004)

2003 Fiscal Year Annual Research Report

ペプチド神経修飾系の生物機能に関する分子から行動レベルまでの横断的研究

Principal Investigator

岡 良隆 東京大学, 大学院・理学系研究科, 教授 (70143360)

Research Products

[Publications] Amano, M., Oka, Y., Yamanome, T., Okuzawa, K., Yamamori, K.: "Immunocytochemical localization and ontogenic development melanin-concentrating hormone in the brain of a pleuronectiform fish, the barfin flounder."Cell and Tissue Research. 311. 71-77 (2003)

[Publications] Kiya, t., Oka, Y.: "Glutamate receptors in the terminal nerve gonadotropin-releasing hormone neurons of the dwarf gourami (teleost)."Neuroscience Letters. 345. 113-116 (2003)

[Publications] Amano, M., Okubo, K., Yamanome, T., Oka, Y., Kawaguchi, N., Aida, K., Yamamori, K.: "Ontogenic development of three GnRH systems in the brain of a pleuronectiform fish, brain flounder."Zoological Science. (in press). (2004)

[Publications] Ishizaki, M., Iigo, M., Amano, M., Oka, Y.: "Different modes of gonadotropin-releasing hormone (GnRH) release from multiple GnRH systems as revealed by radioimmunoassay using brain slices of a teleost, the dwarf gourami (Colisa lalia)."Endocrinology. (in press). (2004)

[Publications] Ishikawa, M., Tsutsui, H., Cosson, J., Oka, Y., Morisawa, M.: "Strategies for sperm chemotaxis in the siphonophores and ascidians : a numerical simulation study."Biological Bulletin. (in press). (2004)

[Publications] Kawahara, R., Imaoka, T., Matsuda, M., Mori, T.: "Up-regulation of thymosin beta 4 gene expression in experimentally-induced uterine adenomyosis in mice."In Vivo. 17. 561-565 (2003)

[Publications] Fujiko Masui, Manabu Matsuda, Takao Mori: "Vitamin A prevents the irreversible proliferation of vaginal epithelium induced by neonatal injection of keratinocyte growth factor in mice."Cell Tiss Res. 311. 251-258 (2003)

[Publications] Ryouka Kawahara, Manabu Matsuda, Takao Mori: "Increase in the number of integrinbeta1-immunoreactive monocyte-lineage cells in experimentally-induced adenomyosis in mice."Life Sci. 73. 907-916 (2003)

[Publications] Manabu Matsuda, Jason A.Lockefeer, Nelson D.Horeseman: "Aldolase C/Zebrin gene regulation by prolactin during pregnancy and loctation."Endocrine. 20. 91-100 (2003)

[Publications] Matsuda, M., Imaoka, T., Vomachka, AJ, Gudelsky, GA, Hou, Z., Mistry, M, Bailey, JP, Nieport, KM, Walther, DJ, Bader, M, Horseman, ND: "Serotonin regulates mammary gland development via an autocrine-paracrine loop."Dev Cell. 6. 193-203 (2003)

[Publications] Hazuki Aikawa, Sachiko Koyama, Manabu Matsuda, Keiko Nakahashi, Yasuhisa Akazome, Takao Mori: "Relief effect of vitamin A on the decreased motility of sperm and the increased incidence of malformed sperm in mice exposed neonatally to bisphenol A."Cell Tiss Res. 315. 119-124 (2003)

[Publications] Manabu Matsuda, Fujiko Masui, Takao Mori: "Neonatal estrogenization leads to increased expression of cellular retinol binding protein 2 in the mouse reproductive tract."Cell Tiss Res. (in press). (2004)

岡良隆東京大学, 大学院・理学系研究科, 教授 (70143360)