Neuropathological study of amyotrophic lateral sclerosis and mutant SOD1 transgenic mice

• Project/Area Number: 18500280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: SASAKI Shoichi Tokyo Women's Medical University, 医学部, 准教授 (40119962)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 筋萎縮性側索硬化症 / 運動ニューロン疾患 / 変異SOD1導入マウス / 脊髄前角 / 後根神経節 / ミトコンドリア / 封入体 / 超微細構造 / SOD1 / 脊髄 / 電子顕微鏡 / 病理 / 運動ニューロン

Research Abstract

孤発性筋萎縮性側索硬化症(ALS)の脊髄前角、後根神経節および家族性ALSの動物モデルである変異SOD1(H46R)導入マウスの脊髄におけるミトコンドリア(Mt)を電子顕微鏡で観察した。孤発性ALS では前角細胞質内のMt 内部に線維状の封入体が、後根神経節のMt 内に縦断面で線維状の、横断面で管状の封入体が、変異SOD1(H46R)導入マウスでは主に軸索のMt内部に電子密度の高い無構造の異常構造物がみられた。これらのMt の形態異常は、筋萎縮性側索硬化症の病態機序にMt の異常が関与していることを示唆している。

Research Products

• [Journal Article] Activation of signal transducer and activator of transcription-3 in the spinal cord of sporadic amyotrophic lateral sclerosis (2009)
  • Author(s): Shibata N, Kakita A, Takahashi H, Ihara Y, Nobukuni K, Fujimura H, Sakoda S, Sasaki S, et.al.
  • Journal Title: Neurodegener Dis 6 Pages: 118-126
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in transgenic mice with an H46R mutant SOD1 gene (2009)
  • Author(s): Sasaki S, Aoki M, Nagai M, Kobayashi M, Itoyama Y.
  • Journal Title: J Neuropathol Exp Neurol 68 Pages: 365-373
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in transgenic mice with an H46R mutant SOD1 gene. (2009)
  • Author(s): Sasaki S, Aoki M, Nagai M, Kobayashi M, Itoyama Y.
  • Journal Title: Journal of Neuropathology and Experimental Neurology (In press)
  • Peer Reviewed
• [Journal Article] Activation of signal transducer and activator of transcription-3 in the spinal cord of sporadic amyotrophic lateral sclerosis patients. (2009)
  • Author(s): Shibata N, Kakita, A, Takahashi H, Ihara Y, Nobukuni K, Fujimura H, Sakoda S, Sasaki S, et al
  • Journal Title: Neurodegenerative Diseases (In press)
  • Peer Reviewed
• [Journal Article] Involvement of the spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonism (2008)
  • Author(s): Sasaki S, Shirata A, Yamane K, Iwata M.
  • Journal Title: Neuropathology 28 Pages: 74-80
  • Peer Reviewed
• [Journal Article] 筋萎縮性側索硬化症の臨床病型 (2008)
  • Author(s): 佐々木彰一
  • Journal Title: 東女医大誌 78
  • NAID: 110007524776
• [Journal Article] 「ALS-臨床と研究の最新情報」 孤発性ALS古典型臨床症候と経過 (2008)
  • Author(s): 佐々木彰一
  • Journal Title: Clinical Neuroscience 26 Pages: 268-269
• [Journal Article] アテローム塞栓症による脊髄梗塞 (2008)
  • Author(s): 橋詰良夫、汪寅、佐々木彰一
  • Journal Title: 脊椎脊髄ジャーナル 21 Pages: 95-98
• [Journal Article] Involvement of the spinal motor neurons in parkin-positive autosomal recessive juvenile Parkinsonism. (2008)
  • Author(s): Sasaki S, Shirata A, Yamane K, Iwata M
  • Journal Title: Neuropatholgy 28 Pages: 74-80
  • Peer Reviewed
• [Journal Article] 注目される感染症 : 診断と治療の進歩. II. 人獣共通感染症. 5. バリアントCJD (2007)
  • Author(s): 佐々木彰一
  • Journal Title: 日本内科学会雑誌 96(11) Pages: 2423-2428
• [Journal Article] 「ALS : 研究と診療の進歩」ALSの病型-臨床と病理- (2007)
  • Author(s): 佐々木彰一
  • Journal Title: BRAIN and NERVE 59(10) Pages: 1013-1021
• [Journal Article] Motor neuron disease in transgenic mice with an H46R mutant SOD1 gene (2007)
  • Author(s): Sasaki S, Nagai M, Aoki M, Komori T, Itoyama Y, Iwata M.
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 517-524
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis (2007)
  • Author(s): Sasaki S, Iwata M.
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 10-16
  • Peer Reviewed
• [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model (2007)
  • Author(s): Shibata N, Kawaguchi M, Uchida K, Kakita A, Takahashi H, Sasaki S, et.al.
  • Journal Title: Neuropathology 27 Pages: 49-61
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis (2007)
  • Author(s): Sasaki S, Horie Y, Iwata M.
  • Journal Title: Acta Neuropathol 114 Pages: 633-639
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis. (2007)
  • Author(s): S. Sasaki, et. al.
  • Journal Title: Acta Neuropathologica 114 Pages: 633-639
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. (2007)
  • Author(s): S. Sasaki and M. Iwata
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 10-16
  • Peer Reviewed
• [Journal Article] Motor neuron disease in transgenic mice with an H46R mutant SOD1 gene. (2007)
  • Author(s): S. Sasaki, et. al.
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 517-524
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. (2007)
  • Author(s): S.Sasaki, et al.
  • Journal Title: Journal of Neuropathology and Experimental Neurology 66・1 Pages: 10-16
• [Journal Article] Parvalbumin and calbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene (2006)
  • Author(s): Sasaki S, Warita H, Komori T, Murakami T, Abe K, Iwata M.
  • Journal Title: Brain Res 2083 Pages: 196-203
  • Peer Reviewed
• [Journal Article] Neuronal inclusions in sporadic motor neuron disease are negative for alpha-synuclein (2006)
  • Author(s): Sasaki S, Komori T, Iwata M.
  • Journal Title: Neurosci Lett 397 Pages: 15-19
  • Peer Reviewed
• [Journal Article] ALS の亜型 (2006)
  • Author(s): 佐々木彰一
  • Journal Title: 臨床神経学 46(11) Pages: 825-827
  • NAID: 10020347267
• [Journal Article] バリアントCJD (2006)
  • Author(s): 佐々木彰一
  • Journal Title: 化学療法の領域 22 Pages: 45-50
• [Journal Article] Neuronal inclusions in sporadic motor neuron disease are negative for alpha-synuclein. (2006)
  • Author(s): S.Sasaki, et al.
  • Journal Title: Neuroscience Letters 397・1-2 Pages: 15-19
• [Journal Article] Parvalbumin and ealbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene. (2006)
  • Author(s): S.Sasaki, et al.
  • Journal Title: Brain Research 1083・1 Pages: 196-203
• [Presentation] 孤発性筋萎縮性側索硬化症の脊髄前角細胞における小胞体の変化 (2009)
  • Author(s): 佐々木彰一,武田貴裕、本間温、内山真一郎
  • Organizer: 第50回日本神経病理学会総会
  • Place of Presentation: 高松
• [Presentation] 孤発性ALSの脊髄前角におけるTDP-43免疫活性の細胞内分布 (2009)
  • Author(s): 佐々木彰一,武田貴裕、本間温、柴田亮行、小林槇雄、内山真一郎
  • Organizer: 第50 回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] Mitochondrial alterations in transgenic mice with an H46R mutant SOD1 gene (2008)
  • Author(s): Sasaki S, Nagai M, Aoki M, Itoyama Y.
  • Organizer: 19^<th> International symposium on ALS/MND
  • Place of Presentation: Birmingham, UK
• [Presentation] H46R変異SOD1導入マウスのミトコンドリア異常 (2008)
  • Author(s): 佐々木彰一,永井真貴子、青木正志、糸山泰人、岩田誠
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] Mitochondrial alterations in transgenic mice with an H46R mutant SOD1 gene. (2008)
  • Author(s): Sasaki S, Nagai M, Aoki M, Itoyama Y.
  • Organizer: 19^<th> International symposium on ALS/MND
  • Place of Presentation: Birmingham
• [Presentation] Mitochondria in dorsal root ganglion cells are affected in sporadic amyotrophic lateral sclerosis (2007)
  • Author(s): Sasaki S, Iwata M
  • Organizer: 18^<th> International symposium on ALS/MND
  • Place of Presentation: Toronto, Canada
• [Presentation] Involvement of the spinal autonomic nervous system in parkin-positive autosomal recessive juvenile parkinsonism (2007)
  • Author(s): Sasaski S, Shirata A, Yamane K, Iwata M.
  • Organizer: 5^<th> Congress of the International Society for Autonomic Neuroscience
  • Place of Presentation: Kyoto, Japan
• [Presentation] 孤発性筋萎縮性側索硬化症の後根神経節におけるミトコンドリアの異常 (2007)
  • Author(s): 佐々木彰一,本間温、広井敦子、柴田亮行、小林槇雄、岩田誠
  • Organizer: 第48回日本神経病理学会総会
  • Place of Presentation: 東京
• [Presentation] H46R変異SOD1導入マウスの病理像 (2007)
  • Author(s): 佐々木彰一,永井真貴子、青木正志、小森隆司、糸山泰人、岩田誠
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] Mitochondria in dorsal root ganglion cells are affected in sporadic amyotrophic lateral sclerosis. (2007)
  • Author(s): S. Sasaki and M. Iwata
  • Organizer: 18th International symposium on ALS/MND.
  • Place of Presentation: Toronto
• [Presentation] Neuronal inclusions in sporadic motor neuron disease are negative for alpha-synuclein (2006)
  • Author(s): Sasaki S, Iwata M.
  • Organizer: 17^<th> International symposium on ALS/MND
  • Place of Presentation: Yokohama, Japan
• [Presentation] Neuronal inclusions in sporadic motor neuron disease are negative for alpha-synuclein (2006)
  • Author(s): Sasaki S, Iwata M
  • Organizer: XI. International congress on neuromuscular disease
  • Place of Presentation: Istanbul, Turkey
• [Book] 筋萎縮性側索硬化症の近況.Year note series. Selected articles.(2010岡庭 豊編) (2009)
  • Author(s): 佐々木彰一
  • Publisher: メディクメディア社,東京
• [Book] Methods in molecular biology volume on “Protein misfolding and cellular stress in disease and ageing. " (2009)
  • Author(s): Sasaki S
  • Publisher: The Humana Press Inc(In press)
• [Book] 筋萎縮性側索硬化症. 「整形外科診療実践ガイド」(守屋秀繁、糸満盛憲、内田淳正、荻野利彦、黒坂昌弘、戸山芳昭編集) (2006)
  • Author(s): 佐々木彰一
  • Publisher: 文光堂、東京
• [Book] 言語聴覚士のための基礎知識。臨床神経学・高次脳機能障害学。 (2006)
  • Author(s): 佐々木彰一
  • Publisher: 医学書院
• [Book] 整形外科診療実践ガイド (2006)
  • Author(s): 佐々木彰一
  • Publisher: 文光堂
• [Book] Protein misfolding and cellular stress in disease and ageing -Concepts and Protocols
  • Author(s): Sasaki S
  • Publisher: Determination of altered mitochondria ultrastructure by electron microscopy(Methods in Molecular Biology. (ed.J. Walker). Humana Press/Springer. (in press))
• [Book] 神経症状と検査異常。8.1) 症状。6. 筋萎縮・筋力低下。チャート病態 内科診断学
  • Author(s): 佐々木彰一
  • Publisher: 中外医学社(印刷中)
• [Book] 老化. サブテキスト神経学
  • Author(s): 佐々木彰一
  • Publisher: 医学書院(印刷中)