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PATHOGENESIS OF DEMENTIA IN AMYOTROPHIC LATERAL SCLEROSIS (ALTERATION OF INOSITOL 1,4,5-TRISPHOSPHATE (IP3) RECETOR AND RYANODINE RECEPTOR IN THE HIPPOCAMPUS)

Research Project

Project/Area Number 05670572
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKEIO UNIVERSITY

Principal Investigator

TANAKA Kotaro  DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,ASSISTANT PROFESSOR, 医学部, 専任講師 (90129528)

Co-Investigator(Kenkyū-buntansha) NAGATA Eiichiro  DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (00255457)
NOZAKI Hiroyuki  DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (80218312)
NOGAWA Shigeru  DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (50208310)
近藤 太郎  慶應義塾大学, 医学部, 助手 (40234942)
白井 俊孝  慶應義塾大学, 医学部, 助手 (80196592)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
KeywordsAMYOTROPHIC LATERAL SCLEROSIS / DEMENTIA / INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR / HIPPOCAMPUS / RYANODINE RECEPTOR / イノシトール1,4,5三リン酸受容体
Research Abstract

We have investigated the role of type 1 inositol 14,5-trisphosphate receptor (IP3R1) in the morphogenesis of the central nervous system and the behavioral development. In mice lacking IP3R1 generated by gene targeting, microscopic examination revealed no abnormality in the histological sections of each structure fo the brain, which were stained by hematoxyline-eosin or anti-microtubule-associated protein 2. Western blot analysis showed that homozygote (IR3R1 -/-) has no IP3R1 protein, but normal amounts of IP3R2 and IP3R3. IP3 binding was significantly reduced all over the brain in the homozygote mice. At postnatal day (PND) of 9, homozygote began to show ataxia. At PND 15, truncal trosion appeared, and repetitive tonic or tonic-clonic seizures prevailed by PND 20-23. Electroencephalogram showed a paroxysmal polyspike activites. Such generalized seizures were suppressed by intraperitoneal injection of pentobarbital or diazepam. Taken together, IP3R1 seems to play an important role in the regulation of not only cerebellar function but also of the excitability of the neural networks.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] NAGATA E,TANAKA K et al.: "Alteration of inositol 1, 4, 5-trisphosphate receptor after six-hour hemispheric ischemia in the gerbil brain" Neuroscience. 61. 983-990 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 永田栄一郎,田中耕太郎 他: "実験的脳虚血におけるイノシトール1, 4, 5三リン酸受容体の変化" 臨床神経. 33. 726-732 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 野崎博之,田中耕太郎 他: "砂ネズミ脳虚血におけるRyanodine受容体の変化に関する研究" 神経化学. 32. 82-83 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] TANAKA K,FUKUUCHI et al.: "Reduction in second-messenger ligand binding sites after brain ischemia." Brain Res Bull. 32. 49-56 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] MATSUMOTO M,NAGATA E,TANAKA K et al.: "Ataxia and epileptic seizures in mice lacking type 1 inositol 1, 4, 5-trisphosphate receptor." Nature. 379. 168-171 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 野崎博之,田中耕太郎 他: "脳虚血における脳内Ca^<2+>誘発性Ca^<2+>放出チャンネルの変化" 脳卒中. 17. 306-314 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tanaka K,Fukuuchi Y,Gomi S et al: "Reduction in second-messenger ligand binding sites after brain ischemia." Brain Res Bull. 32. 49-56 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagata E,Tanaka K,Gomi S et al: "Alteration of inositol 1,4,5-trisphosphate receptor after six-hour hemispheric ischemia in the gerbil brain." Neuroscience. 61. 983-990 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tanaka K,Gomi S,Takashima S et al: "Enhanced maximal binding capacity (Bmax) of second messenger ligand in the acute phase of cerebral ischemia." Neurosci Res. 19. 347-356 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nozaki H,Tanaka K,Shirai T et al: "Alteration of ryanodine receptors after 6-hour hemispheric ischemia in the gerbil brain." Jpn J Stroke. 17. 306-314 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagata E: "Alteration of inositol 1,4,5-trisphosphate receptor binding in the early phase of cerebral ischemia in the gerbil." Auton Nerv System. 32. 119-126 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto M,Nakagawa T,Inoue T,Nagata E,Tanaka K et al: "Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor." Nature. 379. 168-171 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] NAGATA E, TANAKA K et al.: "Alteration of inositol 1,4,5-trisphosphate receptor six-hour hemispheric ischemia in the gerbil braiv." Neuroscience. 61. 983-990 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 永田栄一郎,田中耕太郎他: "実験的脳虚血におけるイノシトール1,4,5三リン酸受容体の変化" 臨床神経. 33. 726-732 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] 野崎博之,田中耕太郎他: "砂ネズミ脳虚血におけるRyanodine受容体の変化に関する研究" 神経化学. 32. 82-83 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] TANAKA K, FUKUUCHI et al.: "Reduction in second-messenger ligand binding sites after brain lschemia." Brain Res Bull. 32. 49-56 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] MATSUMOTO M, NAGATA E, TANAKA K et al.: "Ataxia and epileptic seizures in mice lackinf typel inositol 1,4,5-trisphosphate receptor." Nature. 379. 168-171 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 野崎博之,田中耕太郎他: "脳虚血における脳内Ca^<2+>誘発性Ca^<2+>放出チャンネルの変化" 脳卒中. 17. 306-314 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] NAGATA E.,TANAKA K.,et al: "Alteration of inositol 1.4.5-trisphosphate receptor after six-hour hemispheric ischemia in the gerbil brain21GC01:Neuroscience" 61(4). 983-990 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 永田栄一郎、田中耕太郎、他: "実験的脳虚血におけるイノシトール1、4、5三リン酸受容体の変化21GC02:臨床神経" 33. 726-732 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 野崎博之、田中耕太郎、他: "砂ネズミ脳虚血におけるRyanodine受容体の変化に関する研究" 神経化学. 32. 82-83 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] TANAKA K.,FUKUUCHI Y.,et al: "Reduction in second-messenger ligand binding sites after brain ischemlia" Brain Res Bull. 32. 49-56 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田中耕太郎: "脳虚血とセカンドメッセンジャー系" Annual Review 神経1994. 1994年版. 120-133 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] TANAKA K.,FUKUUCHI Y.,et al.: "Inhibition of hitric. oxide synthesis impairs autoregulation of localcerebral blood flow in the rat." Neuro Report.4. 267-270 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 永田栄一郎、田中耕太郎他: "実験的脳虚血におけるイノシトール1,4,5三リン酸受容体の変化" 臨床神経. 33. 726-732 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 野崎博之、田中耕太郎他: "砂ネズミ脳虚血におけるRyanodine受容体の変化に関する研究" 神経化学. 32. 82-83 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] TANAKA K,FUKUUCHI Y et al.: "Reduction in second-messenger ligand binding sites after brain is chemia" BRAIN RES.BULL.32. 49-56 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 田中耕太郎: "脳虚血とセカンドメッセンジャー系" Annual Review 神経1994. 1994年版. 120-133 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] TANAKA K,FUKUUCHI Y et al: "Inhibition of mitric oxicle Symthesis impairs autoregulation of local cerebral blood flow in the rat." NEVRO REPORT. 4. 267-270 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] TANAKA K,FUKUUCHI Y et al.: "Selective reduction in 〔^3H〕inosifal 1,4,5-trisphosphate binding in the hippacampus CA1 after b-hour experimental cerebral isobemia." STROKE. 24. 163-163 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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