1996 年度実績報告書

線条体障害ラットにおける大脳基底核神経回路網の再構築移植治療に関する実験的研究

研究課題

研究課題/領域番号	08671596
研究機関	熊本大学
研究代表者	後藤恵熊本大学, 医学部附属病院, 講師 (50240916)
研究分担者	永廣信治熊本大学, 医学部附属病院, 講師 (60145315) 生塩之敬熊本大学, 医学部, 教授 (20028583)
キーワード	Striatum / substantia nigra / Cerebral Ischemia / Transplantation / Basal ganglia / Plasticity
研究概要	ラット線条体障害に伴う大脳基底核機能異常を解析すると共に、線条体内胎仔神経細胞移植による神経回路網の再構築を目的として本研究を行った。その結果、線条体に虚血障害が及んだ後、黒質網状層神経細胞に経シナプス性神経細胞死が生ずること、また、緻密層ドパミン作動性神経細胞において、チロシン水酸化酵素の発現の低下が惹起されることを見い出した。そして、これらの黒質細胞の経シナップス性退行変性はGABA agonistの脳室内持続投与により防止された。さらに、この変性過程にはNMDAレセプターも関与しておりそのantagonistであるMK801の投与にて上記の退行変性は防止された。これらの所見より黒質細胞の経シナップス性神経細胞死を抑制しつつ、胎仔線条体神経細胞をラット線条体虚血巣内に移植したところ、有意に黒質神経細胞の変性は防止され、著名な線条体-黒質路の再構築をみた。これに伴い、移植動物において、薬物行動学的異常の改善が得られた。この実験結果は適切な移植組織に対するtarget neuronが存在することにより、移植治療の効果が上がることを示唆している。

研究成果

(12件)

すべてその他

すべて文献書誌 (12件)

[文献書誌] Yamada K,Goto S,et al.: "Involvement of N-methyl-D-aspartate (NMDA) receptor in the delayed transneuronal death of substantia nigra neurons." Brain Research. 743. 233-239 (1996)
[文献書誌] Goto S,et al.: "Intracerebral grafting versus transneuronal degeneration." Kumamoto Medical Journal. (in press).
[文献書誌] Yamada K,Goto S,et al.: "Intraventricular administration of GABA_A receptor agonist muscimol attenuates the exo-focal change of the substantia nigra neurons following transient middle cerebral artery occlusion in rats." Neuropathology. (in press).
[文献書誌] Yamada K,Goto S,et al.: "Intraventricular drug infusion technique with osmotic pump : an application for the in vivo study of the transneuronal degeneration occurring in the rat striatonigral system." Brain Research Protocols. (in press).
[文献書誌] Goto S,et al.: "Posteroventral pallidotomy in a patient with parkinsonism caused by hypoxic encephalopathy." Neurology. (in press).
[文献書誌] Okamura A,Goto S,et al.: "Postnatal ontogeny of the striatal enriched protein tyrosine phosphatase (STEP) in the rat striatum." Experimental Neurology. (in press).
[文献書誌] Yamada K,Goto S,et al.: "GABAergic transmission and tyrosine hydroxylase expression in the nigral dopaminergic neurons : an in vivo study using a reversible ischemia model of rats." Neuroscience. 73. 783-789 (1996)
[文献書誌] Yoshikawa M,Goto S,et al.: "Neurons containing nicotinamide adenine dinucleotide phospate (NADPH) -diaphorase in the organotypic static slice cultures of rat cerebrocortices : Developmental study." Acta Histochemia et Cytochemica. 29. 169-176 (1996)
[文献書誌] Goto S,et al.: "Subregional loss of putaminal efferents to the basal ganglia output nuclei may cause parkinsonism in striatonigral degeneration." Neurology. 47. 1032-1036 (1996)
[文献書誌] Inoue N,Goto S,et al.: "Cytochrome oxidase activity during acute focal ischaemia in rat brain. A pathophysiology of acute focal ischemia : Part 2." Acta Neurochirurgica. 138. 1126-1131 (1996)
[文献書誌] Yamada K,Goto S,et al.: ""Reactive change" of the substantia nigra neurons subsequent to striatal infarction in rats." Biomedical Research. 17. 339-346 (1996)
[文献書誌] Korematsu K,Goto S,et al.: "Time-sequential change in apomorphine-induced rotational behavior following transient middle cerebral artery occlusion in rats." Biomedical Research. 17. 395-398 (1996)

1996 年度 実績報告書

線条体障害ラットにおける大脳基底核神経回路網の再構築移植治療に関する実験的研究

研究代表者

後藤 恵 熊本大学, 医学部附属病院, 講師 (50240916)

研究成果

[文献書誌] Yamada K,Goto S,et al.: "Involvement of N-methyl-D-aspartate (NMDA) receptor in the delayed transneuronal death of substantia nigra neurons." Brain Research. 743. 233-239 (1996)

[文献書誌] Goto S,et al.: "Intracerebral grafting versus transneuronal degeneration." Kumamoto Medical Journal. (in press).

[文献書誌] Yamada K,Goto S,et al.: "Intraventricular administration of GABA_A receptor agonist muscimol attenuates the exo-focal change of the substantia nigra neurons following transient middle cerebral artery occlusion in rats." Neuropathology. (in press).

[文献書誌] Yamada K,Goto S,et al.: "Intraventricular drug infusion technique with osmotic pump : an application for the in vivo study of the transneuronal degeneration occurring in the rat striatonigral system." Brain Research Protocols. (in press).

[文献書誌] Goto S,et al.: "Posteroventral pallidotomy in a patient with parkinsonism caused by hypoxic encephalopathy." Neurology. (in press).

[文献書誌] Okamura A,Goto S,et al.: "Postnatal ontogeny of the striatal enriched protein tyrosine phosphatase (STEP) in the rat striatum." Experimental Neurology. (in press).

[文献書誌] Yamada K,Goto S,et al.: "GABAergic transmission and tyrosine hydroxylase expression in the nigral dopaminergic neurons : an in vivo study using a reversible ischemia model of rats." Neuroscience. 73. 783-789 (1996)

[文献書誌] Yoshikawa M,Goto S,et al.: "Neurons containing nicotinamide adenine dinucleotide phospate (NADPH) -diaphorase in the organotypic static slice cultures of rat cerebrocortices : Developmental study." Acta Histochemia et Cytochemica. 29. 169-176 (1996)

[文献書誌] Goto S,et al.: "Subregional loss of putaminal efferents to the basal ganglia output nuclei may cause parkinsonism in striatonigral degeneration." Neurology. 47. 1032-1036 (1996)

[文献書誌] Inoue N,Goto S,et al.: "Cytochrome oxidase activity during acute focal ischaemia in rat brain. A pathophysiology of acute focal ischemia : Part 2." Acta Neurochirurgica. 138. 1126-1131 (1996)

[文献書誌] Yamada K,Goto S,et al.: ""Reactive change" of the substantia nigra neurons subsequent to striatal infarction in rats." Biomedical Research. 17. 339-346 (1996)

[文献書誌] Korematsu K,Goto S,et al.: "Time-sequential change in apomorphine-induced rotational behavior following transient middle cerebral artery occlusion in rats." Biomedical Research. 17. 395-398 (1996)

1996 年度実績報告書

後藤恵熊本大学, 医学部附属病院, 講師 (50240916)