Investigation of the role of neuronal cell deth in a neurodegenerative prosess of ALS model mice

• Project/Area Number: 25870754
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology; Neurochemistry/Neuropharmacology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Hara Chikako 東京慈恵会医科大学, 医学部, 助教 (40528452)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 筋萎縮性側索硬化症 / 前頭側頭変性症 / ALS / FTLD / 細胞内凝集体 / 神経変性 / 神経変性疾患 / 細胞内凝集体形成 / モデルマウス / 筋委縮性側索硬化症

Outline of Final Research Achievements

We had planed to investigate the abnormal cytoplasmic inclution and neuronal cell deth caused by TAR DNA Binding Protein-43(TDP-43) of ALS model mice. TDP-43 has been identified as a causative gene of both amyotrophic lateral scleosis(ALS) and frontotemporal lober degeneratiion (FTLD), based on the findings that cytoplasmic inclusion bodies in ALS and FTLD pathology.
Details of cytoplasmic inclusion forming processes were investigated by this study. Specificaly, the abnormal flagmentation of TDP-43 protein in cultured cells, the frequency of the abnormal cytoplasmic inclusions, and decrease in number of the spinal cord neuron of the adult ALS model mice were detected.

Research Products

• [Journal Article] Analysis of RNA metabolism in peripheral WBCs of TDP-43 KI mice identifies novel biomarkers of ALS. (2015)
  • Author(s): Hasegawa M., Hara-Miyauchi C., Ohta H., Sakimura K., Okano H., Okano H. J.
  • Journal Title: Neuroscience Research Volume: 106 Pages: 12-22
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] TAR DNA binding protein-43(TDP-43)に変異を持つ筋萎縮性側索硬化症および前頭側頭変性症の動物モデル (2014)
  • Author(s): Chikako Hara-Miyauchi
  • Organizer: 成体脳ニューロン新生懇談会
  • Place of Presentation: 東京大学フューチャーセンター（千葉県柏市）
  • Year and Date: 2014-12-05
• [Presentation] Multimodal and exclusive pathology between ALS and FTLD by TDP-43 mutations (2014)
  • Author(s): Chikako Hara-Miyauchi
  • Organizer: Society for Neuroscience
  • Place of Presentation: ワシントンD.C.
  • Year and Date: 2014-11-16 – 2014-11-20
• [Presentation] Multimodal and exclusive pathology between ALS and FTLD by TDP-43 mutations (2014)
  • Author(s): Chikako Hara-Miyauchi
  • Organizer: 日本神経科学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Patent(Industrial Property Rights)] AMYOTROPHIC LATERAL SCLEROSIS AND/OR FRONTOTEMPORAL LOBAR DEGENERATION MODEL MOUSE (2015)
  • Inventor(s): MIYAUCHI, Chikako
  • Industrial Property Rights Holder: Keio University
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-01-15
  • Overseas