Analysis for factors toxic to motor neurons released from astrocytes expressing ALS-linked mutated SOD1.

• Project/Area Number: 21591083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kitasato University (2010-2011); Okayama University (2009)
• Principal Investigator: NAGAI Makiko 北里大学, 医学部, 講師 (80420488)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 筋萎縮性側索硬化症 / 運動ニューロン / アストロサイト / SOD1 / トランスジェニックマウス / 脊髄 / 神経変性 / トランスジェニックウス / ALS / RNA

Research Abstract

Mutations in superoxide dismutase-1(SOD1) cause a form of the fatal paralytic disorder amyotrophic lateral sclerosis(ALS), presumably by a combination of cell-autonomous and non-cell-autonomous processes. In this study, we identified the cDNAs that expression increased in the primary motor neurons with astrocytes expressing mutated SOD1(G93A) compared to control. Then, we made the transgenic mice with the one of these cDNAs which expressed most in the spinal motor neuron of G93A mice. They did not show the motor neuron death, so this cDNA we used may not cause the neuronal death.

Research Products

• [Journal Article] Parkin-Mediated Protection of Dopaminergic Neurons in a Chronic MPTP-Minipump Mouse Model of Parkinson Disease (2011)
  • Author(s): Yasuda T, Hayakawa H, Nihira T, Ren YR, Nakata Y, Nagai M, Hattori N, Miyake K, Takada M, Shimada T, Mizuno Y, Mochizuki H
  • Journal Title: J Neuropathol Exp Neurol Volume: 70(8) Pages: 686-97
  • Peer Reviewed
• [Journal Article] Comparisons of acoustic function in SCA31 and other forms of ataxias (2011)
  • Author(s): Ikeda Y, Nagai M, Kurata T, Yamashita T, Ohta Y, Nagotani S, Deguchi K, Takehisa Y, Shiro Y, Matsuura T, Abe K
  • Journal Title: Neurol Res Volume: 33(4) Pages: 427-32
  • Peer Reviewed
• [Journal Article] Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis (2011)
  • Author(s): Miyazaki K, Ohta Y, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89(5) Pages: 718-28
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Violeta-Lukic-Panin, Morimoto N, Ohta Y, Nagai M, Ikeda Y, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 31 Pages: 161-70
  • Peer Reviewed
• [Journal Article] Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophie lateral sclerosis (2011)
  • Author(s): Miyazaki K, Ohta Y, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89(5) Issue: 5 Pages: 718-28
  • DOI: 10.1002/jnr.22594
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Panin VL, Morimoto N, Ohta Y, Nagai M, Ikeda Y, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 1371 Pages: 161-70
  • Peer Reviewed
• [Journal Article] Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene (2010)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Ohta Y, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Asanuma M, Abe K
  • Journal Title: J Neurosci Res Volume: 88(8) Pages: 1804-11
  • Peer Reviewed
• [Journal Article] Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene. (2010)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Ohta Y, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Asanuma M, Abe K.
  • Journal Title: J Neurosci Res Volume: 88(8) Pages: 1804-11
  • Peer Reviewed
• [Journal Article] Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation (2009)
  • Author(s): Narai H, Manabe Y, Nagai M, Nagano I, Ohta Y, Murakami T, Takehisa Y, Kamiya T, Abe K
  • Journal Title: Neurol Int Volume: 1(1)
  • Peer Reviewed
• [Journal Article] Spinal anterior horn has the capacity to self-regenerate in amyotrophic lateral sclerosis model mice (2009)
  • Author(s): Miyazaki K, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Abe K
  • Journal Title: J Neurosci Res Volume: 87(16) Pages: 3639-48
  • Peer Reviewed
• [Journal Article] Neuronal NOS and cyclooxygenase-2 contribute to DNA damage in a mouse model of Parkinson disease (2009)
  • Author(s): Hoang T, Choi DK, Nagai M, Wu DC, Nagata T, Prou D, Wilson GL, Vila M, Jackson-Lewis V, Dawson VL, Dawson TM, Chesselet MF, Przedborski S
  • Journal Title: Free Radic Biol Med Volume: 47(7) Pages: 1049-56
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in transgenic mice with an H46R mutant Cu/Zn superoxide dismutase gene (2009)
  • Author(s): Sasaki S, Aoki M, Nagai M, Kobayashi M, Itoyama Y
  • Journal Title: J Neuropathol Exp Neurol Volume: 68(4) Pages: 365-73
  • Peer Reviewed
• [Journal Article] Changes of Nogo-A and receptor NgR in the lumbar spinal cord of ALS model mice (2009)
  • Author(s): Miyazaki K, Nagai M, Ohta Y, Morimoto N, Kurata T, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K
  • Journal Title: Neurol Res Volume: 31(3) Pages: 316-21
  • Peer Reviewed
• [Journal Article] Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SOD1 gene (2009)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Kurata T, Takehisa Y, Ikeda Y, Kamiya T, Okazawa H, Abe K
  • Journal Title: J Neurosci Res Volume: 87(4) Pages: 928-36
  • Peer Reviewed
• [Journal Article] Spinal anterior horn has the capacity to self-regenerate in amyotrophic lateral sclerosis model mice. (2009)
  • Author(s): Miyazaki K, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Abe K
  • Journal Title: J Neurosci Res. 87(16) Pages: 3639-3648
  • Peer Reviewed
• [Journal Article] Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SODI gene. (2009)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Kurata T, Takehisa Y, Ikeda Y, Kamiya T, Okazawa H, Abe K
  • Journal Title: J Neurosci Res. 87(4) Pages: 928-936
  • Peer Reviewed
• [Journal Article] Mitochondrial alterations in transgenic mice with an H46R mutant Cu/Zn superoxide dismutase gene. (2009)
  • Author(s): asaki S, Aoki M, Nagai M, Kobayashi M, Itoyama Y
  • Journal Title: J Neuropathol Exp Neurol. 68(4) Pages: 365-373
  • Peer Reviewed
• [Presentation] ALS剖検脊髄の免疫染色による検討 (2011)
  • Author(s): 永井真貴子, 早川英規, 荻野美恵子, 望月秀樹
  • Organizer: 第52回日本神経学会学術大会
  • Year and Date: 2011-05-18
• [Presentation] ALS患者における黒質神経細胞脱落の検討 (2011)
  • Author(s): 遠藤基, 早川英規, 梁正淵, 永井真貴子, 荻野美恵子, 望月秀樹
  • Organizer: 第52回日本神経学会学術大会
  • Year and Date: 2011-05-18
• [Presentation] ALS剖検脊髄の免疫染色による検討 (2011)
  • Author(s): 永井真貴子, 早川英規, 荻野美恵子, 望月秀樹
  • Organizer: 日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] ALS患者における栄養管理と生命予後 (2009)
  • Author(s): 永井真貴子、出口健太郎、名古谷章子、池田佳生、阿部康二
  • Organizer: 第27回日本神経治療学会総会
  • Year and Date: 2009-06-11
• [Presentation] 運動ニューロンを障害する変異SOD1アストロサイト由来液性因子の解析 (2009)
  • Author(s): 永田哲也, Diane Re, 永井真貴子, Serge Przedborski, 阿部康二
  • Organizer: 第50回日本神経学会学術大会
  • Year and Date: 2009-05-20
• [Book] パーキンソン病の細胞移植・遺伝子治療 (2010)
  • Author(s): 永井真貴子, 望月秀樹
  • Publisher: Medical Science Disest
• [Remarks]
  • URL: http://www.khp.kitasato-u.ac.jp/ska/shinkein/index.html