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Neuropathological examination of amyotrophic lateral sclerosis with special reference to cytopathology of motoneurons

Research Project

Project/Area Number 13670663
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionJichi Medical University

Principal Investigator

NAKANO Imaharu  Jichi Medical School, School of Medicine, Professor, 医学部, 教授 (40092423)

Co-Investigator(Kenkyū-buntansha) KATO Shinsuke  Tottori University, Faculty of Medicine, Institute of Neurological Sciences, Department of Neuropathology, Associate Professor, 医学部, 助教授 (60194817)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordscervical spondylosis / ALS / astrocytes / ALS with dementia / 3D-SSP / ALSのみ / 運動ニューロン / apotosis / カスパーゼカスケード / Caspase-3 / 家族性筋萎縮性側索硬化症(ALS) / 細胞病理像 / Bunina小体 / 硝子様封入体 / 糸束様封入体
Research Abstract

<1>Cervical spondylosis (CS) that can repeatedly insult the cervical cord has been one of the prime suspects of ALS etiology. Neuropathological features that CS itself brings about in the cervical cord, however, are not well differentiated from those of ALS because of rare autopsied cases with such double insults. To clarify the role of CS in pathogenesis of ALS, it is essential to differentiate the CS-from AIS-caused pathology. Then, we examined minutely the neuropathology of the cervical cord in ALS with marked cord compression at a single intervetebral level. The anterior horn was uniformly depleted of the motoneurons through the cervical cord. At the compressed level, the anterior horn neuropil was much more rarefied accompanying denser proliferation of microglia and less reaction of astrocytes, indicating that the spondylotic cord injuries may mainly involve the neuropil with suppression of astrocytic reaction and enhancement of microglial proliferation. <2>Although some patients with ALS show a particular type of dementia, the responsible neuropathology remains to be clarified because the autopsy often fails to show brain pathology that explains it. We performed ^<123>I-IMP-SPECT in 5 cases of ALS with dementia (ALSD), and analyzed the data using 3D-SSP with Z-score. This method revealed obvious reduction of cortical blood flow in the frontal and temporal lobes in ALSD. Neuropathological examination of one autopsied case which died soon after a ^<123>I-IMP-SPECT demonstrated spongy changes of the neuropil and irregular loss of neurons in the 2^<nd> and 3^<rd> cortical layers with marked astrocytosis in the subcortical white matter of the frontal lobe and medial side of temporal tip cortices. The blood flow reduction seen in the cerebral cortex in this condition is supposed to mainly reflect the neuronal loss and neuropil rarefaction in the superficial cerebral cortex.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Tsuchiya K, et al.: "Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists : An additional autopsy case with a clinical course of 19 years."Neuropathology. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, et al.: "Expression of hepatocyte growth factor and c-Met in anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS) : immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation."Acta Neuropathol. 106. 112-120 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lu Y-Y, et al.: "Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport."Neuroscience Research. 45. 33-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang L-J, et al.: "Neuroprotictive effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis."The Jounal of Neuroscience. 22. 6920-6928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, et al.: "Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy : a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions."Neuropathology. 22. 308-316 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, et al.: "Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia : a clinicopathological study of eight autopsy cases."Acta Neuropathol. 104. 249-259 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishihara K, et al.: "Lewy body-free nigral degeneration - a case report."J Nrurol Sci.. 198. 97-100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, et al.: "A typical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease : a report of an autopsy case with a clinical course of 15 years."Acta Neuropathol. 101. 625-630 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, et al.: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusion bodies : a clinical, genetic, and pathological study."Clin Neuropathol. 20. 53-59 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, et al.: "Formation of advanced glycation end-product-modified superoxide dismutase-1(SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation."Neuropathology. 21. 67-81 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中野今治: "ALS--最近の話題「はじめに」"医学の歩み. 205. 117-118 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山崎峰雄 他: "神経疾患-神経変性疾患における神経細胞死はアポトーシスか?-"最新医学. 57. 2481-2486 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中野今治: "筋萎縮性側索硬化症の遺伝子治療-モデル動物での治療実験-"最新医学. 57. 1634-1639 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中野今治: "運動ニューロン疾患"CLINICAL NEUROSCIENCE. 19. 804-806 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano I: "Molecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis."Elsevier Science B.V.Amsterdam. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, et al.: "Molecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis."Elsevier Science B.V.Amsterdam. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, Sano M, Shiotsu H, Akiyama H, Watabiki S, Taki K, Kondo H, Nakano I, Ikeda K: "Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists : An additional autopsy case with a clinical course of 19 years."Neuropathology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, Funakoshi H, Nakamuxa T, Kato M, Nakano I, Himno A, Ohama E: "Expression of heptyte growth factor and c-Met in anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS) : immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation."Acta Neuropathol. 106. 112-120 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lu Y-Y, Wang L-J, Muiamatsu S, Ikeguchi K, Fujimoto K, Okada T, Muzukami H, MatushitaT, Hanazono Y, Kume A, Nagatsu T, Ozawa K, Nakano I: "Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport."Neuroscience Research. 45. 33-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang L-J, Lu Y-Y, Mummatsu S, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Matsushita T, Hanazono Y, Kume A, Nagatsu T, Ozawa K, Nakano I: "Neuroprotictive effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis."The Journal of Neuroscience. 22. 6920-6928 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, Takahashi M, Shiotsu H, Akiyama H, Haga C, Watabiki S, Taki K, Nakano I, Ikeda K: "Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy : a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions."Neuropathology. 22. 308-316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, Ikeda K, Mimura M, Takahashi M, Miyazaki H, Anno M, Shiotsu H, Akabane H, Niizato K, Uchihara T, Tominaga I, Nakano I: "Constant involvement of the l3etz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia a clinicopathological study of eight autops cases."Acta Neuropathol.. 104. 249-259 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishihara K, Nonaka A, Fukui T, Kawamura M, Shiota J, Nakano I: "Lewy body-fire nigral degeneration-a case report."J Nrurol Sci.. 198. 97-100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, Ikeda K, Haga C, Kobayashi T, Moiimatsu Y, Nakano I, Matsushita M: "Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease : a report of an autopsy case with a clinical course of 15 years."Acta Neuropathol.. 101. 625[-630 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, Matsunaga T, Aoki M, Haga C, Ooe K, Abe K, Ikeda K, Nakano I: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusion bodies : a clinical, genetic, and pathological study."Clin Neuropathol.. 20. 53-59 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, Nakashima K, Horiuchi S, Nagai R, Cleveland DV, Liu I, Hirano A, Takikawa M, Kato M, Nakano I, Sakoda S, Asayama K, Ohama E: "Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of the mechamisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation."Neuropathology. 21. 67-81 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato S, Nakashima K, Horiuchi S, Cleveland DW, HiranoA, Takikawa M, Kato M, Naknao I, Sakoda S, Asayama K, Ohama B: "Formation of advanced glycatin endproduct(AGE)-modified superoxide dismutase 1 (SOD1) is common to familial amyotrophic lateral sclerosis (FALS) patients with SOD1 gene mutation and G85R transgenic mice."Molecular Mechanism and Therapeutics of Amyotrophic Lateral Scleosis.(Abe K.(Ed))(Elsevier Science B.V.Amsterdam)(Proceedings of the International Symposium on Melecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis, Japan, 22-24 September 2000). 265-271 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano I: "Pyramidal tract pathology in amyotrophic lateral sclerosis-axon staining reveals degeneration undisclosed on myelin staining-"Molecladar Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis.(Abe K.(ED))(Elsevier Science B.V.Amsterdam)(Proseedings of the International Symposium on Melecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis, Japan, 22-24 September 2000). 3-11 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchiya K, et al.: "Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists : An additional autopsy case with a clinical course of 19 years."Neuropathology. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato S, et al.: "Expression of hepatocyte growth factor and c-Met in anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation."Acta Neuropathol. 106. 112-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lu Y-Y, et al.: "Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport."Neuroscience Research. 45. 33-40 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wang L-J, et al.: "Neuroprotictive effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis."The Journal of Neuroscience. 22. 6920-6928 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy : a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions."Neuropathology. 22. 308-316 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia : a clinicopathological study of eight autopsy cases."Acta Neuropathol. 104. 249-259 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishihara K, et al.: "Lewy body-free nigral degeneration - a case report."J Nrurol Sci.. 198. 97-100 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease : a report of an autopsy case with a clinical course of 15 years."Acta Neuropathol. 101. 625-630 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusion bodies : a clinical, genetic, and pathological study."Clin Neuropathol. 20. 53-59 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato S, et al.: "Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation."Neuropathology. 21. 67-81 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中野今治: "ALS--最近の話題「はじめに」"医学の歩み. 205. 117-118 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山崎峰雄 他: "神経疾患-神経変性疾患における神経細胞死はアポトーシスか?-"最新医学. 57. 2481-2486 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中野今治: "筋萎縮性側索硬化症の遺伝子治療-モデル動物での治療実験-"最新医学. 57. 1634-1639 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中野今治: "運動ニューロン疾患"CLINICAL NEUROSCIENCE. 19. 804-806 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakano I: "Molecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis."Elsevier Science B.V.Amsterdam. (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato S, et al.: "Morecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis."Elsevier Science B.V.Amsterdam. (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Muramatsu S, et al.: "Behavioral recovery in a primate model of Parkinson's disease by triple transduction of striatal cells with adeno-associated viral vectors expressingdopamine-synthesizing enzymes"Hum Gene Ther. 13. 345-354 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang L-J, et al.: "Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease"Gene Ther. 9. 381-389 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang L-J, et al.: "Neuroprotictive effects of glial cell line-derived neurotrophic factor mediated by an adenoassociated virus vector in a transgenic animal model of amyotrophic lateral sclerosis"The Journal of Neurosciene. 22. 6920-6928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada T, et al.: "Adeno-associated virus vectors for gene taransfer to the brain"METHODES. 28. 237-247 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishihara K, et al.: "Lewy body-free nigral degeneration-a case report"J Neurol Sci. 198. 97-100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia : a clinicopathological study of eight autopsy cases"Acta Neuropathol. 104. 249-259 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy : a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions"Neuropathology. 22. 308-316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozawa K, et al.: "Gene therapy for Parkinson's disease using AAV vectors. Mapping the Progress of Alzheimer's and Parkinson's disease"Kluwer Academic/Plenum publishers. 4 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中野 今治: "今日の診断指針、第5班"医学書院、東京、. 2092 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大橋靖雄, 他: "筋萎縮性側索硬化症(ALS)患者の日常活動における機能評価尺度日本版改訂ALS Function rating scaleの検討"BRAIN and NERVE. 53. 346-355 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato S, et al.: "Formation of advanced glycation end-product-modified superoxide dismutase-1 (SOD1) is one of mechamisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation"Neuropathology. 21. 67-81 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Familial amyotrophic lateral sclerosis with posterior column degeneration and basophilic inclusions bodies : a clinical, genetic, and pathological study"Clin Neuropathol.. 20. 53-59 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease : a report of an autopsy case with a clinical course of 15 years"Acta Neuropathol.. 101. 625-630 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Distribution of basal ganglida lesions in generalized variant of Pick's disease : a clinicopathological study of four autopsy cases"Acta Neuropathol.. 102. 441-448 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuchiya K, et al.: "Distribution of cerebral cortical lesions In Pick's disease with Pick bodies : a clinicopathlogogical study of six autopsy cases showing unusual clinical presentations"Acta Neuropathol. 102. 553-571 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中野今治: "ダイナミック神経診断学"西村書店. 732 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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