Analysis of the mutated SOD1 astrocyte-releasing factors toxic to motor neurons

• Project/Area Number: 19590991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: NAGAI Makiko Okayama University, 医学部・歯学部附属病院, 助教 (80420488)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 筋萎縮性側索硬化症 / トランスジェニックマウス / スーパーオキシドディスムターゼ1 / 脊髄 / 初代培養 / アストロサイト / Bax / 筋萎縮性側索硬化症(ALS) / 運動ニューロン / 胚性幹細胞 / 分化誘導 / SOD1 / レチノイド / オートファジー

Research Abstract

本研究ではin vitroの系を用いてグリアからのシグナルが運動ニューロンに与える影響を明らかにした。実験材料として変異SOD1(G93A)を導入したトランスジェニックマウス(筋萎縮性側索硬化症モデルマウス)を用いた。変異SOD1を発現したアストロサイト上の運動ニューロンは生存率が低下、細胞体の面積が小さく軸索が短かった。Bax inhibitorであるV5を培養液に加えることで生存率の低下を抑制でき、細胞毒性の機序としてBaxカスケードの関与が示唆された。

Research Products

• [Journal Article] Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis (2008)
  • Author(s): Ohta Y, Kamiya T, Nagai M, Abe K(他8名)
  • Journal Title: J Neurosci Res 86(13) Pages: 3028-37
  • Peer Reviewed
• [Journal Article] Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis. (2008)
  • Author(s): Ohta Y, Kaniya T. Kagai M, Hagata T, Morimoto N, Miyazaki K. Murakami T. Kurata T, Takehisa Y, Ikeda Y, Asoh S, Ohta S, Abe K.
  • Journal Title: J Neurosci Res. 86(13) Pages: 3028-3037
  • Peer Reviewed
• [Journal Article] Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction. (2008)
  • Author(s): Kurata T, Hayashi T, Muiakami T. Miyazaki K, Morimoto N, Ohia Y, Takthisa Y, Nagai M, Kawarabayashi T, Takao Y, Ohta T, Karigaya Y, Manabe Y, Kamiya T. shoji M, Abe K.
  • Journal Title: Neurol Res 30(8) Pages: 860-867
  • Peer Reviewed
• [Journal Article] 遺伝性ALS (2008)
  • Author(s): 永井真貴子
  • Journal Title: モダンフィジシャン 28 Pages: 1803-1807
• [Journal Article] Intrathecal delivery of hepatocyte growth factor from amyotrophic lateral sclerosis onset suppresses disease progression in rat amyotrophic lateral sclerosis model (2007)
  • Author(s): Ishigaki A, Aoki M, Nagai M, Itoyama Y(他5名)
  • Journal Title: J Neuropathol Exp Neurol 66(11) Pages: 1037-44
  • Peer Reviewed
• [Journal Article] Increased autophagy in transgenic mice with a G93A mutant SOD1 gene (2007)
  • Author(s): Morimoto N, Nagai M, Abe K(他8名)
  • Journal Title: Brain Res 1167 Pages: 112-7
  • Peer Reviewed
• [Journal Article] Motor Neuron Disease in Transgenic Mice With an H46R Mutant SOD1 Gene (2007)
  • Author(s): Sasaki S, Nagai M, Iwata M(他3名)
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 517-524
  • Peer Reviewed
• [Journal Article] Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons (2007)
  • Author(s): Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S
  • Journal Title: Nature Neurosci 10(5) Pages: 615-622
  • Peer Reviewed
• [Journal Article] Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. (2007)
  • Author(s): Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S.
  • Journal Title: Nature Neurosci. 10(5) Pages: 615-622
  • Peer Reviewed
• [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] Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. (2007)
  • Author(s): Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Ahe K.
  • Journal Title: Brain Res. 1167 Pages: 112-117
  • Peer Reviewed
• [Presentation] 変異SOD1遺伝子発現アストロサイトの運動神経細胞死への関与 (2008)
  • Author(s): 永井真貴子
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-15
• [Presentation] 変異SOD1遺伝子発現アストロサイトの運動神経細胞死への関与 (2008)
  • Author(s): 永井真貴子, 宮崎一徳, 森本展年, 倉田智子, 武久康, 池田佳生, 神谷達司, 阿部康二
  • Organizer: 第49回 日本神経学会総会
  • Place of Presentation: 東京
• [Presentation] Dysfunction of mitochondrial oxidative phosphorylation in ALS rat model (2007)
  • Author(s): Nagai M
  • Organizer: The 23^<rd> International symposium on Cerebral Blood Flow and Metabolism
  • Place of Presentation: 大阪
  • Year and Date: 2007-05-22
• [Presentation] Dysfunction of mitochondrial oxidative phosphorylation in ALS rat model. (2007)
  • Author(s): Nagai M, Ohta Y, Morimoto N, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K.
  • Organizer: Brain 07
  • Place of Presentation: Osaka
  • Year and Date: 2007-05-21