Oxidative stress in child-onset neurodegenerative disorders.

• Project/Area Number: 18591175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: TANUMA Naoyuki Tokyo Metropolitan Organization for Medical Research, 東京都神経科学総合研究所, 研究員 (00281676)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Masaharu 東京都医学研究機構, 東京都神経科学総合研究所, 副参事研究員 (00280777)
• 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: 酸化ストレス / 神経変性疾患 / 急性脳症 / 重症心身障害 / ELISA / 免疫組織化学染色 / 抗酸化療法 / MELAS / タウ蛋白 / 色素性乾皮症 / DRPLA / 重症心身障害児(者) / 肝脂肪変性 / 有熱時けいれん重積・群発 / 海馬硬化症 / Lafora病 / 8-OHdG

Research Abstract

小児期発症神経変性疾患の神経変性に酸化ストレスが関与していることを明らかにするために、ELISA法による生体試料(尿、髄液)中の酸化ストレスマーカー測定と剖検脳を用いた神経病理学的解析を行った。その結果、Lafora病、歯状核赤核淡蒼球ルイ体萎縮症DRPLA、色素性乾皮症XPなどの神経変性に酸化ストレスが関与していることが明らかになった。また、重症心身障害の呼吸障害や肝脂肪変性、急性脳症やけいれん重積症においても酸化ストレスの関与が示唆され、これらの治療のための抗酸化療法の開発が望まれる。

Research Products

• [Journal Article] Oxidative stress in developmental brain disorders. (2009)
  • Author(s): Hayashi M.
  • Journal Title: Neuropathology 29 Pages: 1-8
  • NAID: 10025824645
  • Peer Reviewed
• [Journal Article] 色素性乾皮症・コケイン症候群の神経変性機序と治療の試み (2009)
  • Author(s): 林雅晴
  • Journal Title: 医学のあゆみ 228 Pages: 143-146
• [Journal Article] Oxidative stress in developmental brain disorders (2009)
  • Author(s): Hayashi M.
  • Journal Title: Neuropathology 29 Pages: 1-8
  • NAID: 10025824645
  • Peer Reviewed
• [Journal Article] Role of oxidative stress in xeroderma pigmentosum. Adv. (2008)
  • Author(s): Hayashi M.
  • Journal Title: Exp. Med. Biol. 637 Pages: 120-127
  • Peer Reviewed
• [Journal Article] 重症心身障害者の肝脂肪変性における酸化ストレス-予備的検討- (2008)
  • Author(s): 八谷靖夫、林雅晴、田沼直之
  • Journal Title: 脳と発達 40 Pages: 381-385
  • NAID: 10024845599
  • Peer Reviewed
• [Journal Article] Oxidative stress as a biomarker of respiratory disturbance in patients with severe motor and intellectual disabilities. (2008)
  • Author(s): Tanuma N, Miyata R, Hayashi M, Uchiyama A, Kurata K.
  • Journal Title: Brain Dev. 30 Pages: 402-409
  • NAID: 10025577167
  • Peer Reviewed
• [Journal Article] Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy. (2008)
  • Author(s): Miyata R, Hayashi M, Tanuma N, Shioda K, Fukatsu R, Mizutani S.
  • Journal Title: J. Neurol. Sci. 264 Pages: 133-139
  • Peer Reviewed
• [Journal Article] 重症心身障害者の肝脂肪変性における酸化ストレス-予備的検討- (2008)
  • Author(s): 八谷靖夫, 林雅晴, 田沼直之
  • Journal Title: 脳と発達 40 Pages: 381-385
  • NAID: 10024845599
  • Peer Reviewed
• [Journal Article] Role of oxidative stress in xeroderma pigmentosum (2008)
  • Author(s): Hayashi M.
  • Journal Title: Adv. Exp. Med. Biol. 637 Pages: 120-127
  • Peer Reviewed
• [Journal Article] Oxidative stress as a biomarker of respiratory disturbance in Patients with severe motor and intellectual disabilties. (2008)
  • Author(s): Tanuma N, Miyata R, Hayashi M, Uchiyama A, Kurata K.
  • Journal Title: Brain Dev. 30 Pages: 402-409
  • Peer Reviewed
• [Journal Article] Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy. (2008)
  • Author(s): Miyata R, Hayashi M, Tanuma N, Shioda K, Fukatsu R, Mizutani S.
  • Journal Title: J Neurol Sci. 264 Pages: 133-139
  • Peer Reviewed
• [Journal Article] 重症心身障害児(者)の肝脂肪変性における酸化ストレス-予備的検討 (2008)
  • Author(s): 八谷 靖夫、林 雅晴、田沼 直之.
  • Journal Title: 脳と発達 40-4(in press)
  • Peer Reviewed
• [Journal Article] Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. (2006)
  • Author(s): Tanuma N, Sakuma H, Sasaki A, Matsumoto Y.
  • Journal Title: Acta Neuropathol. 112 Pages: 195-204
  • Peer Reviewed
• [Journal Article] 多発性硬化症の病変形成機構とケモカインの役割 (2006)
  • Author(s): 田沼直之、松本陽
  • Journal Title: 神経研究の進歩 50 Pages: 627-635
• [Journal Article] Acute encephalopathy with status epilepticus: Bilateral mesial temporal and claustral lesions, associated with a peripheral marker of oxidative DNA damage. (2006)
  • Author(s): Shiihara T, Kato M, Ichiyama T, Takahashi Y, Tanuma N, Miyata R, Hayasaka K.
  • Journal Title: J. Neurol. Sci. 250 Pages: 159-161
  • Peer Reviewed
• [Journal Article] Acute encephalopathy with status epilepticus : Bilateral mesial temporal and claustral lesions, associated with a peripheral marker of oxidative DNA damage. (2006)
  • Author(s): Shiihara T, Kato M, Ichiyama T, Takahashi Y, Tanuma N, Miyata R, Hayasaka K
  • Journal Title: J. Neurol. Sci. 250 Pages: 159-161
• [Journal Article] Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. (2006)
  • Author(s): Tanuma N, Sakuma H, Sasaki A, Matsumoto Y
  • Journal Title: Acta Neuropathol 112 Pages: 195-204
• [Journal Article] 多発性硬化症の病変形成機構とケモカインの役割 (2006)
  • Author(s): 田沼直之, 松本 陽
  • Journal Title: 神経研究の進歩 50 Pages: 627-635
• [Journal Article] 色素性乾皮症・コケイン症候群の神経変性機序と治療の試み.
  • Author(s): 林雅晴
  • Journal Title: 医学のあゆみ 228 Pages: 2009-2009
• [Presentation] (2008)
  • Author(s): 田沼直之、宮田理英、林雅晴、久保田雅也、高梨潤一、奥村彰久
  • Organizer: 第50回日本小児神経学会総会
  • Place of Presentation: ホテル日航東京(東京)
  • Year and Date: 2008-05-30
• [Presentation] 急性脳症における髄液タウ蛋白の測定 (2008)
  • Author(s): 田沼直之, 宮田理英, 林雅晴, 久保田雅也, 高梨潤一, 奥村彰久
  • Organizer: 第50回日本小児神経学会総会
  • Place of Presentation: ホテル日航東京(東京)
  • Year and Date: 2008-05-30
• [Presentation] 髄液タウ蛋白が高値を示した二峰性けいれんと遅発性拡散能低下を呈する急性脳症の1例 (2008)
  • Author(s): 田沼直之、宮田理英、林雅晴、熊田聡子
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2008-04-26
• [Presentation] Oxidative stress biomarkers in febrile seizures. (2008)
  • Author(s): Tanuma N, Miyata R, Hayashi M, Kubota M.
  • Organizer: The 11^<th> Annual Meeting of the Infantile Seizure Society. International Symposium on Febrile Seizures and Related Conditions.
  • Place of Presentation: ロイヤルオークホテル(大津)
  • Year and Date: 2008-04-10
• [Presentation] Oxidative stress biomarkers in febrile seizures (2008)
  • Author(s): Tanuma N., Miyata R., Hayashi M., Kubota M.
  • Organizer: The 11^<th> Annual Meeting of the Infantile Seizure Society. International Symposium on Febrile Seizures and Related Conditions
  • Place of Presentation: ロイヤルオークホテル(大津)
  • Year and Date: 2008-04-10
• [Presentation] Cerebrospinal fluid levels of oxidative stress markers in patients with prolonged/repetitive febrile seizures. (2007)
  • Author(s): Tanuma N, Miyata R, Hayashi M, Kubota M.
  • Organizer: The 3^<rd> Congress of Asian Society for Pediatric Research.
  • Place of Presentation: 学術情報センター(東京)
  • Year and Date: 2007-10-07
• [Presentation] Cerebrospinal fluid levels of oxidative stress markers in patients with prolonged/repetitive febrile seizures. (2007)
  • Author(s): Tanuma N, Miyata R, Hayashi M, Kubota M.
  • Organizer: The 3rd Congress of Asian Society for Pediatric Research
  • Place of Presentation: 学術情報センター(東京)
  • Year and Date: 2007-10-07
• [Presentation] 有熱時けいれん重積/群発における髄液酸化ストレスマーカー (2007)
  • Author(s): 田沼直之、宮田理英、林雅晴、久保田雅也
  • Organizer: 第49回日本小児神経学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2007-07-06
• [Presentation] Chemokine gradients play a role in lesional expansion of secondary progressive multiple sclerosis. (2006)
  • Author(s): Tanuma N, Sakuma H, Matsumoto Y.
  • Organizer: The 8^<th> International Congress of Neuroimmunology
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2006-10-16
• [Presentation] Oxidative stress in patients with severe motor and intellectual disabilities. (2006)
  • Author(s): Tanuma N, Hachiya Y, Miyata R, Hayashi M.
  • Organizer: 10^<th> International Child Neurology Congress.
  • Place of Presentation: モントリオール(カナダ)
  • Year and Date: 2006-06-12
• [Presentation] 色素性乾皮症における酸化的障害~ELISA法による酸化ストレスマーカー測定の予備的検討~ (2006)
  • Author(s): 田沼直之、宮田理英、林雅晴、由井崇子、荒木聡
  • Organizer: 第48回日本小児神経学会総会
  • Place of Presentation: 東京ベイホテル東急(浦安)
  • Year and Date: 2006-06-01
• [Presentation] Lafora病の神経変性に関する神経病理学的検討 (2006)
  • Author(s): 田沼直之、八谷靖夫、濱野喜美子、宮田理英、林雅晴
  • Organizer: 第109回日本小児科学会学術集会
  • Place of Presentation: ホテル日航金沢(金沢)
  • Year and Date: 2006-04-21