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2000 Fiscal Year Final Research Report Summary

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

Project Period (FY) 1998 – 2000
KeywordsGlutamate receptor ε2 / Autoantibodies / chronic progressive epileptia partialis continua of childhood / Epitope analysis / Glutamate receptor δ2
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.

  • Research Products

    (35 results)

All Other

All Publications (35 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)

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

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

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Yukitoshi Takahashi, Tateki Fujiwara, Kazuichi Yagi, et al.: "Photosensitive epilepsies and pathophysiological mechanisms of photoparoxysmal responese."Neurology. 53. 926-932 (1999)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Yukitoshi Takahashi, Takeshi Ozawa, Hitoshi Nakamura, et al.: "Longwavelength red light emission from TV and photosensitive seizures."Acta Neurol Scand. (in press). (2000)

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  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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  • [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)

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Published: 2002-03-26  

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