1989 年度実績報告書

老化など脳病変修復機序の研究:残存ニュ-ロンの機能保持を求める

研究課題

研究課題/領域番号	62304040
研究機関	新潟大学
研究代表者	生田房弘新潟大学, 脳研究所, 教授 (20018592)
研究分担者	豊倉康夫都老人医療センター, 院長, 東京大学名誉教授 (50009875) 井原康夫東京都老人総合研究所, 臨床第2生理, 室長 (60114386) 萬年徹東京大学, 医学部, 教授 (10010208) 永井克孝東京大学, 医学部, 教授 (80072974) 朝長正徳東京大学, 医学部, 教授 (10072977)
キーワード	アルツハイマ-病 / Sprouting / Bunina 小体 / アストロサイト / GFAP / ガングリオシド
研究概要	本研究は神経細胞が死滅した後の修復機序を明らかにし、脳機能保持の道を求めることを目的としている。平成元年度も、神経細胞の変性・脱落後生じてゆく「病巣の修復過程」に焦点をあててきた。即ち、(朝長)はリン酸化タウ蛋白抗体を用い神経細胞変性が神経突起にも生じていることを認めた。(井原)はアルツハイマ-病脳にみられるカ-リ-ファイバ-がsproutingによるとする仮説を検証するため、PHFにはMAP5という胎児型微小管蛋白が結合していることを明らかとし、上記の仮説の正当性を支持する重要な知見を得た。(萬年)は老人斑における前駆蛋白を検討し、それが110-130KDaの膜分画に存在することを知った。(生田)はウイルス感染脳でも神経細胞壊死の場合においても他の乏血性脳病変と同様、浮腫液中でアストロサイトの移動が生じ、残存神経細胞が再被覆される基本的過程のあることを知った。また、運動神経疾患に特異的に認められるBunina小体が神経細胞小胞体から生じてくることを解明した。これは100余年原因不明の本疾患がある特定の原因によって生じていることを示す極めて大きな意味を持っている。(熊西)は神経細胞が壊死に陥った際にはアストロサイトのGFAP発現も増加することを認めた。この理由を明らかにするためヒトGFAPcDNAのクロ-ンを分離しその塩基配列を決定した。それに基づきGFAP遺伝子クロ-ンを分離した。(平井)はDOPAと鉄の共存で活性酸素を介さずに過酸化脂質が生成され、これが神経細胞を障害することを認めた。(永井)は神経突起伸展効果を示すガングリオシドGQlbの作用が、新しい型の細胞表面局在型プロテンインキナ-ゼを介して発動される証拠を求め得た。(伊藤)は小脳プルキンエ細胞の可塑性-長期抑圧-の主要な過程を明らかにした。

研究成果
(43件)

すべてその他

すべて文献書誌 (43件)

[文献書誌] Wakabayashi,Koichi: "Tyrosine hydroxylase-immunoreactive intrisic neurons in Auerbach´s and Meissner´s Plexuses of humans." Neurosci Lett. 96. 259-263 (1989)
[文献書誌] Oyanagi,Kiyomitsu: "Evidence for sequential degeneration of the neurons in the intermediate zone of the spinal cord in amyotrophic lateral sclerosis:a topographic and quantitative investigation." Acta Neuropathol. 77. 343-349 (1989)
[文献書誌] 若林孝一: "パ-キンソン病の病理形態学" 治療学. 22. 255-258 (1989)
[文献書誌] 生田房弘: "多発性硬化症(MS)" 脊椎脊髄. 2. 253-256 (1989)
[文献書誌] Kawai,Kensuke: "Ultracytochemical study of capillary Ca^<2+>ーATPase activity in brain edema." Acta Neuropathol. 77. 449-454 (1989)
[文献書誌] 小柳清光: "筋萎縮性側索硬化症(ALS)" 脊椎脊髄. 2. 335-338 (1989)
[文献書誌] Takeda,Shigeki: "Adrenoleukodystrophy-Early ultrastructural changes in the brain." Acta Neuropathol. 78. 124-130 (1989)
[文献書誌] Wakabayashi,Koichi: "Occurrence of neurofibrillary tangles in the celiac ganglia." Acta Neuropathol. 78. 448 (1989)
[文献書誌] 若林孝一: "大脳新皮質における多数の老人斑の出現を特徴とし皮質下諸核の神経細胞脱落を欠く老年期痴呆の一剖検例" 臨床神経. 29. 1163-1167 (1989)
[文献書誌] Oyanagi,Kiyomitsu: "Correlative decrease of large neurons in the neostriatum and basal nucleus of Meynert in Alzheimer´s disease." Brain Res. 504. 354-357 (1989)
[文献書誌] Wakabayashi,Koichi: "Lewy bodies in the enteric nervous system in Parkinson´s disease." Arch Histol Cytol. 52(Suppl). 191-194 (1989)
[文献書誌] Takahashi,Hitoshi: "Occurrence of 15-nm-wide straight tubules in neocortical neurons in progressive supranuclear palsy." Acta Neuropathol. 79. 233-239 (1989)
[文献書誌] Uchida,Yoko: "Neurotrophic action of Alzheimer´s disease brain extract is due to the loss of inhibitory factors for survival and neurite formation of cerebral cortical neurons." Brain Res. 481. 190-193 (1989)
[文献書誌] 朝長正徳: "アルツハイマ-病の病因と病理" 日本内科学会雑誌. 78. 1576-1580 (1989)
[文献書誌] 難波吉雄: "抗ネキシン抗体によるAlzheimer型痴呆脳の免疫組織化学" 医学のあゆみ. 151. 613-614 (1989)
[文献書誌] 田中真: "老齢マウス脊髄後根神経節培養細胞に及ぼす神経成長因子とガングリオシドの効果〜神経突起伸長効果の定量的検討〜" 日本医誌. 26. 563-567 (1989)
[文献書誌] 外松明美: "3価鉄ド-パ複合体による生体膜リン脂質過酸化反応" 神経化学. 28. 362-363 (1989)
[文献書誌] 田中真: "レボドパおよびドパミンによる鉄依存性培養神経細胞障害" 神経化学. 28. 354-355 (1989)
[文献書誌] Mori,H.: "A distinct from of tau is selectively incorporated into Alzheimer´s paired helical filaments." Biochem Biophys Res Commun. 159. 1221-1226 (1989)
[文献書誌] Takio,K.: "Identification of beta protein precursor in newborn rat brain." Biochem Biophys Res Commun. 160. 1296-1301 (1989)
[文献書誌] Ihara,Yasuo: "Polypeptide composition of paired helical filaments." Ann Med. 21. 121-125 (1989)
[文献書誌] Ihara,Yasuo: "What mediate between beta-amyloid and paired helical filaments?" Neurobiol Aging. 10. 573-574 (1989)
[文献書誌] 西山明子: "ヒトGFAP cDNAの単離とヒトglioma株におけるGFAP発現の検討" 脳腫瘍病理. 6. 125-131 (1989)
[文献書誌] 西山明子: "バイオテクノロジ-素材としての培養細胞:ヒト癌細胞(II)神経膠腫U-251 MG" 蛋白核酸酵素. 34. 78-79 (1989)
[文献書誌] Nishiyama,Akiko: "Differential expression of glial fibrillary acidic Protein in human glioma" Acta Neuropathol. 78. 9-15 (1989)
[文献書誌] Kumanishi,Toshiro: "Primary malignant lymphoma of the brain:demonstration of immunoglobulin gene rearrangements in four cases by the Southern blot hybridization technique" Acta Neuropathol. 79. 23-26 (1989)
[文献書誌] Kumanishi,Toshiro: "Human GFAP cDNA:cloning and sequence analysis of the coding and the non-coding regions." Acta Neuropathol.
[文献書誌] Onda Kiyoshi: "Establishment of GFAP-positive human glioma cell lines." Acta Neuropathol.
[文献書誌] Nagai,Yoshitaka: "Bioactive ganglioside-mediated carbohydrate recognition in coupling with ecto-protein phosphorylation." 1989 Caebohydrate recognition in cellular function.Wiley,Chichester(Ciba Foundation Symposium 145). 145. 119-134 (1989)
[文献書誌] Nagai,Yoshitaka: "The roles of gangliosides in carbohydrate recognition and signal transduction(novel,ganglioside-dependent ecto protein phosphorylation)" J Neurochem. 52. S4 (1989)
[文献書誌] Tsuji,S.: "Analysis of ecto-protein kinase activities on the cell surface of several neuronal and glia-like cell lines." J Neurochem. 52. S186 (1989)
[文献書誌] Itonori,S.: "Involvement of the acyl chain of ceramide in carbohydrate recognition by an anti-glycolipid monoclonal antibody:the case of an anti-melanoma antibody,M2590,to G_<m3>ーganglioside." Glycoconjugate J. 6. 551-560 (1989)
[文献書誌] Ito,J.: "Induction of astroglial growth inhibition and differentiation by sialosyl cholesterol." Brain Res. 481. 335-343 (1989)
[文献書誌] Kusunoki,S.: "Discrimination of human dorsal root ganglion cells by anti-fucosyl GM1 antibody" Brain Res. 494. 391-395 (1989)
[文献書誌] Kusunoki,S.: "Motor dominant neuropathy and IgM paraproteinemia:the IgM M-protein binds to specific gangliosides." J Neuroimmunol. 21. 177-181 (1989)
[文献書誌] 宇川義一: "Magneto-electrical stimulation(MES法)-磁気刺激による中枢運動系検査法-" 臨床神経. 29. 8-12 (1989)
[文献書誌] Matsumura,K: "The immunological homology between two filamentous cross-linker phosphoproteins,connectin and cross-bridge region of neurofilament-H,is not affected by the phosphorylation state." J Biochem. 105. 226-230 (1989)
[文献書誌] Nakanishi,T.: "Second interim report of the nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of Parkinsonian patients." European Neurology. 29. 3-8 (1989)
[文献書誌] Ono,S.: "Intracytoplasmic inclusion bodies of the thalamus and the substantia nigra,and Marinesco bodies in myotonic dystrophy:a quantitative morphological study." Acta Neuropathol. 77. 350-356 (1989)
[文献書誌] 苅田典生: "局在する大脳病変を示したadrenomyeloneuropathy" 臨床神経学. 29. 483-487 (1989)
[文献書誌] Ito,Masao: "Long-term depression" Ann Rev Neurosci. 12. 85-102 (1989)
[文献書誌] Ito,Masao: "Long-term desensitization of quisqualate-specific glutamate receptors in Purkinje cells investigated with wedge recording from rat cerebellar slices." Neurosci Res. 7. 168-171 (1989)
[文献書誌] Ito,Masao: "Molecular mechanisms of long-term depression in the cerebellum" Brain Signal Transduction and Memory(eds.Ito,M & Y.Nishizuka). 199-212 (1989)

1989 年度 実績報告書

老化など脳病変修復機序の研究:残存ニュ-ロンの機能保持を求める

研究代表者

生田 房弘 新潟大学, 脳研究所, 教授 (20018592)

研究成果

[文献書誌] Wakabayashi,Koichi: "Tyrosine hydroxylase-immunoreactive intrisic neurons in Auerbach´s and Meissner´s Plexuses of humans." Neurosci Lett. 96. 259-263 (1989)

[文献書誌] Oyanagi,Kiyomitsu: "Evidence for sequential degeneration of the neurons in the intermediate zone of the spinal cord in amyotrophic lateral sclerosis:a topographic and quantitative investigation." Acta Neuropathol. 77. 343-349 (1989)

[文献書誌] 若林孝一: "パ-キンソン病の病理形態学" 治療学. 22. 255-258 (1989)

[文献書誌] 生田房弘: "多発性硬化症(MS)" 脊椎脊髄. 2. 253-256 (1989)

[文献書誌] Kawai,Kensuke: "Ultracytochemical study of capillary Ca^<2+>ーATPase activity in brain edema." Acta Neuropathol. 77. 449-454 (1989)

[文献書誌] 小柳清光: "筋萎縮性側索硬化症(ALS)" 脊椎脊髄. 2. 335-338 (1989)

[文献書誌] Takeda,Shigeki: "Adrenoleukodystrophy-Early ultrastructural changes in the brain." Acta Neuropathol. 78. 124-130 (1989)

[文献書誌] Wakabayashi,Koichi: "Occurrence of neurofibrillary tangles in the celiac ganglia." Acta Neuropathol. 78. 448 (1989)

[文献書誌] 若林孝一: "大脳新皮質における多数の老人斑の出現を特徴とし皮質下諸核の神経細胞脱落を欠く老年期痴呆の一剖検例" 臨床神経. 29. 1163-1167 (1989)

[文献書誌] Oyanagi,Kiyomitsu: "Correlative decrease of large neurons in the neostriatum and basal nucleus of Meynert in Alzheimer´s disease." Brain Res. 504. 354-357 (1989)

[文献書誌] Wakabayashi,Koichi: "Lewy bodies in the enteric nervous system in Parkinson´s disease." Arch Histol Cytol. 52(Suppl). 191-194 (1989)

[文献書誌] Takahashi,Hitoshi: "Occurrence of 15-nm-wide straight tubules in neocortical neurons in progressive supranuclear palsy." Acta Neuropathol. 79. 233-239 (1989)

[文献書誌] Uchida,Yoko: "Neurotrophic action of Alzheimer´s disease brain extract is due to the loss of inhibitory factors for survival and neurite formation of cerebral cortical neurons." Brain Res. 481. 190-193 (1989)

[文献書誌] 朝長正徳: "アルツハイマ-病の病因と病理" 日本内科学会雑誌. 78. 1576-1580 (1989)

[文献書誌] 難波吉雄: "抗ネキシン抗体によるAlzheimer型痴呆脳の免疫組織化学" 医学のあゆみ. 151. 613-614 (1989)

[文献書誌] 田中真: "老齢マウス脊髄後根神経節培養細胞に及ぼす神経成長因子とガングリオシドの効果〜神経突起伸長効果の定量的検討〜" 日本医誌. 26. 563-567 (1989)

[文献書誌] 外松明美: "3価鉄ド-パ複合体による生体膜リン脂質過酸化反応" 神経化学. 28. 362-363 (1989)

[文献書誌] 田中真: "レボドパおよびドパミンによる鉄依存性培養神経細胞障害" 神経化学. 28. 354-355 (1989)

[文献書誌] Mori,H.: "A distinct from of tau is selectively incorporated into Alzheimer´s paired helical filaments." Biochem Biophys Res Commun. 159. 1221-1226 (1989)

[文献書誌] Takio,K.: "Identification of beta protein precursor in newborn rat brain." Biochem Biophys Res Commun. 160. 1296-1301 (1989)

[文献書誌] Ihara,Yasuo: "Polypeptide composition of paired helical filaments." Ann Med. 21. 121-125 (1989)

[文献書誌] Ihara,Yasuo: "What mediate between beta-amyloid and paired helical filaments?" Neurobiol Aging. 10. 573-574 (1989)

[文献書誌] 西山明子: "ヒトGFAP cDNAの単離とヒトglioma株におけるGFAP発現の検討" 脳腫瘍病理. 6. 125-131 (1989)

[文献書誌] 西山明子: "バイオテクノロジ-素材としての培養細胞:ヒト癌細胞(II)神経膠腫U-251 MG" 蛋白核酸酵素. 34. 78-79 (1989)

[文献書誌] Nishiyama,Akiko: "Differential expression of glial fibrillary acidic Protein in human glioma" Acta Neuropathol. 78. 9-15 (1989)

[文献書誌] Kumanishi,Toshiro: "Primary malignant lymphoma of the brain:demonstration of immunoglobulin gene rearrangements in four cases by the Southern blot hybridization technique" Acta Neuropathol. 79. 23-26 (1989)

[文献書誌] Kumanishi,Toshiro: "Human GFAP cDNA:cloning and sequence analysis of the coding and the non-coding regions." Acta Neuropathol.

[文献書誌] Onda Kiyoshi: "Establishment of GFAP-positive human glioma cell lines." Acta Neuropathol.

[文献書誌] Nagai,Yoshitaka: "Bioactive ganglioside-mediated carbohydrate recognition in coupling with ecto-protein phosphorylation." 1989 Caebohydrate recognition in cellular function.Wiley,Chichester(Ciba Foundation Symposium 145). 145. 119-134 (1989)

[文献書誌] Nagai,Yoshitaka: "The roles of gangliosides in carbohydrate recognition and signal transduction(novel,ganglioside-dependent ecto protein phosphorylation)" J Neurochem. 52. S4 (1989)

[文献書誌] Tsuji,S.: "Analysis of ecto-protein kinase activities on the cell surface of several neuronal and glia-like cell lines." J Neurochem. 52. S186 (1989)

[文献書誌] Itonori,S.: "Involvement of the acyl chain of ceramide in carbohydrate recognition by an anti-glycolipid monoclonal antibody:the case of an anti-melanoma antibody,M2590,to G_<m3>ーganglioside." Glycoconjugate J. 6. 551-560 (1989)

[文献書誌] Ito,J.: "Induction of astroglial growth inhibition and differentiation by sialosyl cholesterol." Brain Res. 481. 335-343 (1989)

[文献書誌] Kusunoki,S.: "Discrimination of human dorsal root ganglion cells by anti-fucosyl GM1 antibody" Brain Res. 494. 391-395 (1989)

[文献書誌] Kusunoki,S.: "Motor dominant neuropathy and IgM paraproteinemia:the IgM M-protein binds to specific gangliosides." J Neuroimmunol. 21. 177-181 (1989)

[文献書誌] 宇川義一: "Magneto-electrical stimulation(MES法)-磁気刺激による中枢運動系検査法-" 臨床神経. 29. 8-12 (1989)

[文献書誌] Matsumura,K: "The immunological homology between two filamentous cross-linker phosphoproteins,connectin and cross-bridge region of neurofilament-H,is not affected by the phosphorylation state." J Biochem. 105. 226-230 (1989)

[文献書誌] Nakanishi,T.: "Second interim report of the nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of Parkinsonian patients." European Neurology. 29. 3-8 (1989)

[文献書誌] Ono,S.: "Intracytoplasmic inclusion bodies of the thalamus and the substantia nigra,and Marinesco bodies in myotonic dystrophy:a quantitative morphological study." Acta Neuropathol. 77. 350-356 (1989)

[文献書誌] 苅田典生: "局在する大脳病変を示したadrenomyeloneuropathy" 臨床神経学. 29. 483-487 (1989)

[文献書誌] Ito,Masao: "Long-term depression" Ann Rev Neurosci. 12. 85-102 (1989)

[文献書誌] Ito,Masao: "Long-term desensitization of quisqualate-specific glutamate receptors in Purkinje cells investigated with wedge recording from rat cerebellar slices." Neurosci Res. 7. 168-171 (1989)

[文献書誌] Ito,Masao: "Molecular mechanisms of long-term depression in the cerebellum" Brain Signal Transduction and Memory(eds.Ito,M & Y.Nishizuka). 199-212 (1989)

1989 年度実績報告書

生田房弘新潟大学, 脳研究所, 教授 (20018592)