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神経活動による遺伝子発現とその制御機構

Research Project

Project/Area Number 07279107
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionOkazaki National Research Institutes

Principal Investigator

小幡 邦彦  岡崎国立共同研究機構, 生理学研究所, 教授 (60013976)

Co-Investigator(Kenkyū-buntansha) 三木 直正  大阪大学, 医学部, 教授 (40094445)
岡本 仁  理化学研究所, 脳科学総合研究センター, チームリーダー (40183769)
古市 貞一  東京大学, 医科学研究所, 助教授 (50219094)
白尾 智明  群馬大学, 医学部, 教授 (20171043)
池中 一裕  岡崎国立共同研究機構, 生理学研究所, 教授 (00144527)
SAFFEN David  東京大学, 医学部, 助教授 (50231329)
御子柴 克彦  東京大学, 医科学研究所, 教授 (30051840)
Project Period (FY) 1995 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥146,300,000 (Direct Cost: ¥146,300,000)
Fiscal Year 1998: ¥30,100,000 (Direct Cost: ¥30,100,000)
Fiscal Year 1997: ¥36,300,000 (Direct Cost: ¥36,300,000)
Fiscal Year 1996: ¥34,400,000 (Direct Cost: ¥34,400,000)
Fiscal Year 1995: ¥45,500,000 (Direct Cost: ¥45,500,000)
Keywords遺伝子発現 / グルタミン酸レセプター / 小脳顆粒細胞 / カリウムチャネル / GABA / モルヒネ依存 / ドレブリン / 細胞骨格蛋白 / ゼブラフィッシュ / ノックアウトマウス / 最初期遺伝子 / モルヒネ / 転写因子 / 眼胞形成 / 最初期遺伝子zif268 / 薬物依存 / シナプトタグミン / 遺伝子 / 神経発生 / 脳可塑性 / アストロサイト / けいれん / 情報伝達
Research Abstract

脳形成過程ではいったん作られた神経結合が神経活動によって固定化、強化、排除されて、神経ネットワークの完成に至る。また完成後も神経活動によって神経ネットワークが修飾をうけて脳機能の長期的変化が起こる。これは脳可塑性と呼ばれ、いわゆる記憶から運動学習、薬物依存等にわたる。このような脳可塑性の基盤には遺伝子発現を介する物質レベルの持続的、長期的変化があると考えられるが、まだほとんど解明されていないので、7名の研究者によりこの問題に取り組んだ。本年度の成果として、1)小脳の生後発達。顆粒細胞の分化、移動、成熟が起こる際に、KチャネルのうちKv4.2の発現が増加して活動電位が発達すること(池中)、および新規分子Cupidinが発現することを見いだした(古市)。cupidinはHomer/Veslファミリーに属し、グルタミン酸レセプターとアクチン細胞骨格をつないで神経回路発達に与る。2)シナプスの形成と可逆的変化。アクチン結合蛋白ドレブリンがシナプス形成にともなってアイソフォーム変換し樹状突起スパインに局在化するが、この局在性はNMDA型グルタミン酸レセプターの過剰活動で消失する(白尾)。3)神経発生へのGABAの関与。これは最近ラット細胞についての各種培養実験から主張されているので、遺伝子ノックアウトでGABAを消失させたマウスの脳をしらべたところ、正常に組織形成が進行していた(小幡)。GABAの存在しないC.elegans変異種でも神経系形成は正常という最近の知見と対応する。4)麻薬中毒の分子機構。モルヒネを慢性投与したマウスの脳ではPurαの一本鎖DNA結合活性が減少し、この結合活性化因子はカルモジュリンである。モルヒネの依存形成にカルシウム・カルモジュリンを介する遺伝子発現が関与することを示唆した(三木)。

Report

(4 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Ji,F.Y.,Kanbara,N. and Obata,K.: "GABA and Histogenesis in fetal and neonatal mouse brain lacking both the isoforms of glutamic acid decarboxylase." Neuroscience Research. 33-3(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ji,F.Y. and Obata,K.: "Development of the GABA system in organotypic culture of hippocampal and cerebellar slices from 67 kDa isoform of glutamic acid decarboxylase(GAD67)deficient mice." Neuroscience Research. 33-3(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,K.,Suzuki,K. and Shirao,T.: "Rapid conversion of drebrin isoforms during synapse formation in primary culture of cortical neurons." Devel.Brain Res.111. 137-141 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Konishi,Y.,et al.: "Transcriptional regulation of mouse type 1 inositol 1,4,5-trisphosphate receptor gene by Neuro D-related factor." J.Neurochem.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibata,R.,et al.: "Expression of Kv3.1 and Kv4.2 genes in developing cerebellar granule cells." Dev.Neurosci.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuo,C.H,et al.: "Calmodulin functions as an activator of Pur α binding to single-stranded purine rich DNA elements(PUR elements)." Biochem.Biophys.Res.Comm.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 岡本 仁、池中一裕、小幡邦彦、白尾智明: "Neural Development(K.Uyemura,K.Kawamura,T.Yazaki,eds.)" Springer-Verlag,Tokyo, 544 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 岡本 仁: "神経系の発生 神経系の領域化と細胞特異化脳と神経(分子神経生物学入門)(金子章道、川村光毅、植村慶一編)" 共立出版(印刷中), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obata K.: "Excitatory and trophic action of GABA and related substances in newborn mice and organotypic cerehellar culture." Dev Neurosci. 19. 117-119 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Asada H.et al.: "Cleft palate and decreased brain γ-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase." Proc Natl Acad Sci USA. 94. 6496-6499 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoneshima H.et al.: "Ca^<2+> differentially regulates the ligand-affinity states of type 1 and type 3 inositol 1.4.5-trisphosphate receptors." Biochem J.322. 591-596 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ding Y.et al.: "Characterization of a nuclear factor that enhances DNA binding activity of ssCRE-BP/PUR α,a single-stranded DNA binding protein." Neurochem Internat. 31. 45-54 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kikuchi Y.et al.: "Ocular and cerebellar defects in zebrafish induced by overexpression of the LIM domain of the Islet-3 LIM/homeodomain protein." Neuron. 18. 369-382 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mieda M.et al.: "Expression of the rat m4 muscarinic acetylcholine receptor gene is regulated by the neuron-restrictive silencer element/repressor element 1." J Biol Chem. 272. 5854-5860 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小幡邦彦, 他: "ノックアウトマウス・データブック(野口 茂 他編)" 中山書店, 564 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kikuchi Y.et al.: "Molecular Basis of Axon Growth and Nerve Pattern Formation (Fujisawa,H.ed.)" Scientific Societies Press, 280 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Asada et al.: "Mice lacking the 65kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but susceptible to seizures." BBRC. 229. 891-895 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yamaguchi et al.: "Myelin proteolipid protein (PLP),but not DM-20,is an inositol hexakisphosphate binding protein." J.Biol.Chem. 271. 27838-27846 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Hayashi et al.: "Modulatory role of drebrin on the cytoskeleton within dendritic spines in rat cerebral cortex." J.Neuroscience. 15. 7161-7170 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Mieda et al.: "Promoter region of the rat m4 muscarinic receptor gene contains a cell typespecific silencer element." J.Biol.Chem.271. 5177-5182 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Fukuda et al.: "Phospholipid composition dependence Ca^<2+>-dependent phospholipid binding to the C2A domain of synaptotagmin IV" J.Biol.Chem.271. 30303-30306 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Shimoda et al.: "Mermaid : a family of short interspersed repetitive elements widespread in yertebrates." BBRC. 220. 226-232 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokumoto M.et al.: "Molecular heterogeneity among primary motoneurons and within myotomes revealed by differential mRNA expression of novellsl-1 homologs in embryonic zebrafish." Devel.Biol.171. 578-589 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ikemoto M.et al.: "Decrease in CRE-binding activity by chronic morphine administration in mouse brain." Neuro Report. 6. 262-264 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirota J.et al.: "Kinetics of calcium release by immunoaffinity-purified inositol 1,4,5-trisphosphate receptor in reconstituted lipid vesicles." J.Biol.Chem.270. 19046-19051 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishimaru M.et al.: "Methamphetamine-induced dopaminergic hyperactivity is not accompanied with increase in tyrosine hydroxylase mRNA of the rat midbrain." Neurosci.Lett.191. 107-110 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobayashi S.et al.: "K252a,a potent inhibitor of protein kinases,inhibits the migration of cerebellar granule cells in vitro." Dev.Brain Res.90. 122-128 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumoto M.et al.: "Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-triphosphate receptor." Nature. 379. 168-171 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirota J.et al.: "Genes for development,cell growth and infectious dieseases" John Libbey EUROTEXT, 262 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyawaki A.et al.: "Proceedings of the Yamada Conference XXXIX on Calcium as Coll Signal April 26-28,1994 Tokyo,Japan" IGAKU-SHOIN, 293 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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