Determination of common mechanisms shared by multiple types of spinocerebellar ataxia

• Project/Area Number: 24590407
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Gunma University
• Principal Investigator: NAKAMURA KAZUHIRO 群馬大学, 医学(系)研究科(研究院), 准教授 (10327835)
• Co-Investigator(Kenkyū-buntansha): IKOTA Hayato 群馬大学, 大学院医学系研究科, 講師 (90420116) ; 田中 優子 群馬大学, 医学(系)研究科(研究院), 助教 (00533233) ; 中里 洋一 群馬大学, 医学(系)研究科(研究院), 教授 (10106908)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ポリグルタミン病 / ポリグルタミン / 脊髄小脳変性症

Outline of Final Research Achievements

Among various types of the spinocerebellar ataxia, autosomal-dominantly inherited polyglutamine diseases are the most frequent types and are caused by the expansion of a CAG trinucleotide repeat in the coding region of causative genes. Because expanded polyglutamine tract is shared by multiple types of polyglutamine diseases, I tryed to look for the cotribution of expanded polyglutamine itself to neurodegeneration. I produced transgenic (Tg) mice that overexpress 69 repeated glutamine in cerebellar purkinje cells (PCs). The polyglutamine aggregates were seen as early as 2 weeks old, and extensive PC loss was observed at 3 months old in the Tg mice. An observation that injection of a drug that stabilizes microtubule into the Tg mice reduced the number of PC death in some lobules in the cerebellum might suggest involvement of microtubule in PC death seen in polyglutamine diseases.

Research Products

• [Journal Article] Cranial Irradiation Induces Bone Marrow-derived Microglia to the Adult Mouse Brain Tissue (2014)
  • Author(s): Noriyuki OKONOGI,, Kazuhiro NAKAMURA, Yoshiyuki SUZUKI, MD, PhD1; Nana SUTO2; Kazutomo SUZUE, Takuya KAMINUMA, Takashi NAKANO and Hirokazu HIRAI
  • Journal Title: Journal of Radiation Research Volume: 未定
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells ameliorate cerebellar pathology in a mouse model of spinocerebellar ataxia type 1 (2014)
  • Author(s): Matsuura S, Shuvaev AN, Iizuka A, Nakamura K, Hirai H
  • Journal Title: Cerebellum Volume: 未定
  • Peer Reviewed
• [Journal Article] Mutant ataxin-3 with an abnormally expanded polyglutamine chain disrupts dendritic development and metabotropic glutamate receptor signaling in mouse cerebellar purkinje cells (2014)
  • Author(s): Konno A, Shuvaev AN, Miyake N, Miyake K, Iizuka A, Matsuura S, Huda F, Nakamura K, Yanagi S, Shimada T, Hirai H.
  • Journal Title: Cerebellum Volume: 13 Issue: 1 Pages: 29-41
  • DOI: 10.1007/s12311-013-0516-5
  • Peer Reviewed
• [Journal Article] Impairment of spinal motor neurons in spinocerebellar ataxia type 1-knock-in mice. (2013)
  • Author(s): Takechi Y, Mieda T, Iizuka A, Toya S, Suto N, Takagishi K, Nakazato Y, Nakamura K, Hirai H.
  • Journal Title: Neurosci. Lett. Volume: 535 Pages: 67-72
  • DOI: 10.1016/j.neulet.2012.12.057
  • Peer Reviewed
• [Journal Article] cis phosphorylated tau as the earliest detectable pathogenic conformation in Alzheimer disease, offering novel diagnostic and therapeutic strategies. (2013)
  • Author(s): Nakamura K, Zhou XZ, Lu KP
  • Journal Title: Prion Volume: 7 Issue: 2 Pages: 117-120
  • DOI: 10.4161/pri.22849
  • Peer Reviewed
• [Journal Article] Prolyl isomerase Pin1 regulates neuronal differentiation via β-catenin. (2012)
  • Author(s): Nakamura K, Kosugi I, Lee DY, Hafner A, Sinclair DA, Ryo A, Lu KP.
  • Journal Title: Mol. Cell Biol. Volume: 32 Issue: 15 Pages: 2966-78
  • DOI: 10.1128/mcb.05688-11
  • Peer Reviewed
• [Presentation] Mesenchymal stem cell therapy of spinocerebellar ataxia type 1 model mice (2015)
  • Author(s): Kazuhiro Nakamura
  • Organizer: 日本生理学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 脊髄小脳変性症１型モデルマウス中枢および末梢神経障害に対する間葉系幹細胞の治療効果 (2014)
  • Author(s): 中村和裕、平井宏和
  • Organizer: 日本生理学会
  • Place of Presentation: 鹿児島
• [Presentation] 遺伝性脊髄小脳変性症１型ノックインマウスにおける末梢神経障害 (2013)
  • Author(s): 中村 和裕、平井 宏和
  • Organizer: 第３回国際放射線神経生物学会
  • Place of Presentation: 名護、沖縄
• [Presentation] 頭部への局所照射とBone Marrow Derived Microglia(BMDM)の誘導 (2013)
  • Author(s): 小此木範之、中村和裕、鈴木義行、神沼拓也、須藤奈々、中野隆史、平井宏和
  • Organizer: 第３回国際放射線神経生物学会
  • Place of Presentation: 名護、沖縄
• [Presentation] Cranial Irradiation Induces Migration of Bone Marrow Derived Microglia (BMDM) to the Cerebellum in Adult C57BL/6 Mice. (2012)
  • Author(s): Okonogi N, Nakamura K, Suzuki Y, Suto N, Kaminuma T, Nakano T and Hirai H.
  • Organizer: The American Society for Therapeutic Radiology and Oncology 54th annual meeting.
  • Place of Presentation: Boston, MA, USA