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Early diagnosis and treatment of diseases in central nervous system caused by auto-antibodies against glutamate receptors

Research Project

Project/Area Number 10670722
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionUniversity of Tokyo (2000)
Gifu University (1998-1999)

Principal Investigator

MISHINA Masayoshi (2000)  University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80144351)

高橋 幸利 (1998-1999)  岐阜大学, 医学部・附属病院, 講師 (70262764)

Co-Investigator(Kenkyū-buntansha) 三品 昌美  東京大学, 大学院・医学系研究科, 教授 (80144351)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsGlutamate receptor ε2 / Autoantibodies / chronic progressive epileptia partialis continua of childhood / Epitope analysis / Glutamate receptor δ2 / グルタミン酸受容体 / てんかん / 自己免疫疾患 / 傍腫瘍症候群 / ラスムッセン症候群
Research Abstract

(1) The autoantibodies against whole GluR ε2 molecules
The autoantibodies were studied in the sera of 41 epileptic patients (chronic progressive epileptia partialis continua of childhood, 8 ; West syndrome, 15 ; Lennox syndrome, 9 ; Localization-related epilepsy, 9) and six controls. Seven of eight patients with chronic progressive epileptia partialis continua of childhood had autoantibodies (IgG and/or IgM) against GluR ε 2, but IgA-type autoantibodies were not detected. The patient without the autoantibodies was studied at the late stage after the disappearance of epileptia partialis continua. The patient whose serum showed absence of anti-GluR3 autoantibodies in another institute, had autoantibodies against GluR ε 2 in this study. The autoantibodies were not detected in the sera of patients with West syndrome, Lennox-Gastaut syndrome, or localization-related epilepsy, and in those of controls.
(2) Epitope analyses
Epitope analyses showed the autoantibodies were against c-terminal of GluR ε 2 in seven patients, and that additional autoantibodies against n-terminal were shown in a patients transiently. The epitope on c-terminal was near the trans-membrane region.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (66 results)

All Other

All Publications (66 results)

  • [Publications] Inoue, M. et al.: "Enhanced nociception by exogenous and endogenous substance P given into the spinal cord in mice lacking NR2A/ε1, an NMDA receptor subunit."Br. J. Pharmacol. 129. 239-241 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mishina, M.: "Molecular diversity, structure, and function of glutamate receptor channels."Handbook of Experimental Pharmacology. 147. 393-414 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, I. et al.: "Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses."Neuropharmacology. 39. 943-951 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Minami, T. et al.: "Characterization of nociceptin/or phanin FG-induced pain responses in conscious mice : Neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRε subunit knockout mice."Neuroscience. 97. 133-142 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hironaka, K. et al.: "The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor δ2 and ε subunits."J. Biol. Chem.. 275. 16167-16173 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuda, I. and Mishina, M.: "Identification of a juxtamembrane segment of the glutamate receptor δ2 subunit required for the plasma membrane localization."Biochem. Biophys. Res. Commun.. 275. 565-571 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura, K. et al.: "Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule."Eur. J. Neurosci.. 13. 179-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakazawa, T. et al.: "Characterization of Fyn-mediated tyrosine phosphorylation sites on GluRε2 (NR2B) subunit of the N-methyl-D-aspartate receptor."J. Biol. Chem.. 276. 693-699 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto, Y. et al.: "Hyperfunction of dopaminer gic and serotoner gic neural systems in mice lacking NMDA receptor ε1 subunit."J. Neurosci.. 21. 750-757 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uchino, S. et al.: "Real-time two-dimensional visualization of ischemia-induced glutamate release from hippocampal slices."Eur. J. Neurosci.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kishimoto, Y. et al.: "Long-trace interval eyeblink conditioning is impaired in mutant mice lacking the NMDA receptor subunit ε1."Eur. J. Neurosci.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kishimoto, Y. et al.: "Classical eyeblink conditioning in glutamate receptor subunit δ2 mutant mice is impaired in the delay paradigm but not in the trace paradigm."Eur. J. Neurosci.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitayama, K. et al.: "Purkinje cell specific and inducible gene recombination system generated from C57BL/6 mouse ES cells."Biochem. Biophys. Res. Commun.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Hidemoto Kubota, Tateki Fujiwara, et al.: "Epileptia partialis continua of childhood involving bilateral brain hemispheres."Search on Epilepsy. 5(4). 94-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Mori, Toshiya Manabe, Masayoshi Mishina, et al.: "Role of the carboxyl-terminal region of the GluRepsilon2 subunit in synaptic localization of the NMDA receptor channel."Neuron. 21. 571-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Kiyama, Hisashi Mori, Masayoshi Mishina, et al.: "Increased thresholds for long-term potentiation and contextual learning in mice lacking the NMDA-type glutamate receptor epsilonl subunit."J.Neurosci. 18. 6704-6712 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eiharu Morikawa, Hisashi Mori, Masayoshi Mishina, et al.: "Attenuation of focal ischemic brain injury in mice deficient in the epsilonl (NR2A) subunit of NMDA receptor."J.Neurosci. 18. 9727-9732 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Isao Ito, Kenji Sakimura, Masayoshi Mishina, et al.: "Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the epsilonl subunit gene."Neurosci.Res. 30. 119-123 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T Yamakura, Kenji Sakimura, Masayoshi Mishina, et al.: "Sensitivity of the N-methyl-D-aspartate receptor channel to butyrophenones is dependent on the epsilon2 subunit."Neuropharmacology. 37. 709-717 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I Mizuta, Masahiko Watanabe, Masayoshi Mishina, et al.: "Developmental expression of NMDA receptor subunits and the emergence of glutamate neurotoxicity in primary cultures of murine cerebral neurons."Cell.Mol.Life Sci. 54. 721-725 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Hisashi Mori, Masayoshi Mishina, et al.: "Early diagnosis and treatment in intractable epileptic patients with auto-antibodies to glutamate receptor"Ann Rep JphEpi Res Found. 11. 45-52 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Tateki Fujiwara, Kazuichi Yagi, et al.: "Photosensitive epilepsies and pathophysiological mechanisms of photoparoxysmal responese."Neurology. 53. 926-932 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Tateki Fujiwara, Kazuichi Yagi, et al.: "Wavelength dependency of photoparoxysmal responses in photosensitive epileptic patients."Epilepsia. 40(suppl.4). 23-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takashi Hayashi, Hisashi Umemori, Masayoshi Mishina, et al.: "The AMPA receptor interacts with and signals through the protein tyrosine kinase Lyn."Nature. 397. 72-76 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mika Tsujita, Hisashi Mori, Masayoshi Mishina, et al.: "Cerebellar granule cellspecific and inducible expression of Cre recombinase in the mouse."J.Neurosci. 19. 10318-10323 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shinji Mizuno, Yukitoshi Takahashi, Zenichiro Kato, et al.: "Magnetic resonance spectroscopy of tubers in patients with tuberous sclerosis."Acta Neurol Scand.. 102. 175-178 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Takeshi Ozawa, Hitoshi Nakamura, et al.: "Photosensitive seizures induced by animated TV program called "Pocket Monsters" and Long-wavelength red light from CRT."Epilepsia. 41(suppl.9). 62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiaki Doi, Wataru Abo, Yukitoshi Takahashi, et al.: "Milder childhood form of very long-chain acyl-CoA dehydrogenase deficiency in a 6-year-old Japanese boy."Eur J Pediatrics. 159(12). 908-911 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Hisashi Mori, Masayoshi Mishina, et al.: "Auto-antibodies against glutamate receptor ε2 in patients with chronic progressive epilepsia partialis continua of childhood."Epilepsia. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Minako Aoki, Yukitoshi Takahashi, Yuka Miwa, et al.: "Improvement of neurological symptoms by enzyme replacement therapy for Gaucher disease type III b"Eur J Pediatrics. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiyuki Fukao, Yukitoshi Takahashi, Akiko Hirano, et al.: "Myopathic form of very-long chain acetyl-CoA dehydrogenase deficiency : Evidence for tempaerature-sensitivre mild mutations in both mutant alleles in a Japanese girl"Pediatric Research. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Takeshi Ozawa, Hitoshi Nakamura, et al.: "Longwavelength red light emission from TV and photosensitive seizures."Acta Neurol Scand. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Kazuko Sukegawa, Minako Aoki, et al.: "Evaluation of accumulated mucopolysaccharides in the brain of patients with mucopolysaccharidoses by ^1H-magnetic resonance spectroscopy before and after BMT."Pediatric Research. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukitoshi Takahashi, Hisashi Mori, Masayoshi Mishina, et al.: "Epitope analysis of auto-antibodies against GluR ε2 in patients with chronic progressive epileptia partialis continua of childhood."Epilepsia. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masayoshi Mishina: "Molecular diversity, structure, and function of glutamate receptor channels, in "Handbook of Experimental Pharmacology, 147 : Pharmacology of lonic Channel Function" (Endo, M., Kurachi, Y and Mishina, M., eds)"Springer-Verlarg, Berlin. 391-412 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue,M. et al.: "Enhanced nociception by exogenous and endogenous substance P given into the spinal cord in mice lacking NR2A/ε1, an NMDA receptor subunit."Br.J.Pharmacol.. 129. 239-241 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mishina,M.: "Molecular diversity, structure, and function of glutamate receptor channels."Handbook of Experimental Pharmacology. 147. 393-414 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito,I. et al.: "Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses."Neuropharmacology. 39. 943-951 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Minami,T. et al.: "Characterization of nociceptin/orphanin FG-induced pain responses in conscious mice : Neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRε subunit knockout mice."Neuroscience. 97. 133-142 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hironaka,K. et al.: "The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor δ2 and ε subunits."J.Biol.Chem.. 275. 16167-16173 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuda,I.and Mishina,M.: "Identification of a juxtamembrane segment of the glutamate receptor δ2 subunit required for the plasma membrane localization."Biochem.Biophys.Res.Commun.. 275. 565-571 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura,K. et al.: "Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule."Eur.J.Neurosci.. 13. 179-189 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakazawa,T. et al.: "Characterization of Fyn-mediated tyrosine phosphorylation sites on GluRε2 (NR2B) subunit of the N-methyl-D-aspartate receptor."J.Biol.Chem.. 276. 693-699 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto,Y. et al.: "Hyperfunction of dopaminergic and serotonergic neural systems in mice lacking NMDA receptor ε1 subunit."J.Neurosci.. 21. 750-757 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchino,S. et al.: "Real-time two-dimensional visualization of ischemia-induced glutamate release from hippocampal slices."Eur.J.Neurosci.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kishimoto,Y. et al.: "Long-trace interval eyeblink conditioning is impaired in mutant mice lacking the NMDA receptor subunit ε1."Eur.J.Neurosci.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kishimoto,Y. et al.: "Classical eyeblink conditioning in glutamate receptor subunit δ2 mutant mice is impaired in the delay paradigm but not in the trace paradigm."Eur.J.Neurosci.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitayama,K. et al.: "Purkinje cell specific and inducible gene recombination system generated from C57BL/6 mouse ES cells."Biochem.Biophys.Res.Commun.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋幸利: "グルタミン酸受容体自己抗体による難治性てんかんの早期診断・治療"てんかん治療研究振興財団研究年報. 11. 45-52 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yukitoshi Takahashi: "Photosensitive epilepsies and pathophysiological mechanisms of photopuruxysml response"Neurology. 53. 926-932 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yukitoshi Takahashi: "Wavelength dependency of photoparoxysmal responses in photosensitive epileptic patients"Epilepsia. 40(S4). 23-27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Hayashi: "The AMPA receptor interacts with and signals through the protein tyrosine kinase Lyn"Nature. 397. 72-76 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Tsugita: "Corebellar granull cell-specific and inducible expression of Cre recombinase in the mouse"J Nlurosci. 19. 10318-10323 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Sakata: "Modulation by L-and D-isoforms of aminoacids of the L-glutamate rosponse of N-methyl-D-aspartate receptors"Biochemistry. 38. 10099-10106 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi Y.: "Epilepsia Partialis Continua of childhood incolving both brain hemispheres" Search on epilepsy. 5・4. 94-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahashi Y.: "Wavelength dependency of photoparoxysmal responses in photosensitive enileptic patiemts" Epilepsia. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi T.: "The AMPA receptor interacts with and signals through the protein tyrosine kinate lyn." Nature. 397. 72-76 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori H.: "Role of the carboxyl-terminal region of the GluRe2 subumit in synaptic localzatron of the NMOA receptor channel" Neuron. 21. 571-580 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ito I.: "Distribution and Development of NMDA receptor activities at hippocompal synapses examined using mice lacking the El cubunit gene" Neurosci Res. 30. 119-123 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamakura T.: "Sensitivity of the N-methyl-O-Asporecce receptor chunnnele to butyrophenones is dependent on the E2 subunit" Neurophammacology. 37. 709-717 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyama Y: "Increased thresholds for long-term potentiation and confextual leavning in mice lacking the NMDA-type glutamate receptor E1 subunit" J Neurosci. 18. 6704-6712 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuta I: "Developmental expression of NMDA receptor subunits and the emergence of glutomate neurotoxicety in primary cultures of murine carebrol neibors" Cell.Mol.Life Sci. 54. 721-725 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Munemoto Y.: "Auditory pathway and cubitory bruntem response in mice lacking NMDA receptor/E1 and E4 subunits" Neurosci Left.251. 101-104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitahara T.: "Unilateval labyrin the ctomy douinregulates glutomare receptor a-2 expression in the rat vestiblo cerebellunr" Mol Brain Res. 61. 170-178 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morikawa E.: "Attention of focal ischemic brain injury in mice deficient in the E1 (NR2A)subunit of NMDA receptor" J.Neurosci. 18. 9727-9732 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高橋幸利: "アニメ“ポケモン"による光退的反応多発に関する視聴環境調査" てんかん研究. 17・1(印刷中). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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