Myelin disruption in early stages of demyelination

• Project/Area Number: 16K07023
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Yoshida Shigetaka 旭川医科大学, 医学部, 教授 (20230740)
• Co-Investigator(Kenkyū-buntansha): 板東 良雄 秋田大学, 医学系研究科, 教授 (20344575) ; 野村 太一 旭川医科大学, 医学部, 助教 (70756551)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脱髄 / 多発性硬化症 / オリゴデンドロサイト / クプリゾン / パルブアルブミン / 髄鞘 / プロテアーゼ

Outline of Final Research Achievements

Demyelination occurs in multiple sclerosis, ischemia and post-injury. Demyelination affects axons and neural cell bodies. It is important to see changes in early stages of demyelination.
Experimental allergic encephalomyelitis (EAE) was induced in wild-type and KLK-knockout mice. KLK6-KO mice showed milder symptoms than wild-type mice. In early stages of EAE, wild type mice showed many abnormal myelins. In wild-type mice, the expressions of MMP2 and MMP6 were increased, which were not observed in KLK-KO. Cuprizone was used to see the changes of microglia in the corpus callosum. The increase of Iba1 immunoreactivity was observed in cuprizone demyelination.

Academic Significance and Societal Importance of the Research Achievements

脱髄は多発性硬化症をはじめとする脱髄疾患のみならず、虚血や外傷後にも生じ、神経軸索と神経細胞自体にも大きな影響を与える。この最初期にオリゴデンドロサイトおよび髄鞘の変化が認められることを見出したことが、この研究の最大の意義である。これは、脱髄疾患の治療法の創出につながる重要な知見である。

Research Products

• [Journal Article] Pathological changes in mice with long term cuprizone administration (2019)
  • Author(s): Nomura T, Bando Y, Nakazawa H, Kanemoto S, Yoshida S.
  • Journal Title: Neurochemistry International Volume: 126 Pages: 229-238
  • DOI: 10.1016/j.neuint.2019.03.018
  • Peer Reviewed
• [Journal Article] Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis (2018)
  • Author(s): Bando Y, Hagiwara Y, Suzuki Y, Yoshida K, Aburakawa Y, Kimura T, Murakami C, Ono M, Tanaka T, Jiang Y-P, Mitrovi B, Bochimoto H, Yahara O, Yoshida S
  • Journal Title: Glia Volume: 66 Issue: 2 Pages: 359-378
  • DOI: 10.1002/glia.23249
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Yokukansan reduces cuprizone-induced demyelination in the corpus callosum through anti-inflammatory effects on microglia (2017)
  • Author(s): Nomura T, Bando Y, You H, Tanaka T, Yoshida S
  • Journal Title: Neurochemical Research Volume: 42 Issue: 12 Pages: 3525-3536
  • DOI: 10.1007/s11064-017-2400-z
  • Peer Reviewed
• [Presentation] 抗MOG自己抗体がオリゴデンドロサイトに及ぼす影響の解析 (2017)
  • Author(s): 板東良雄、吉田成孝
  • Organizer: 第122回日本解剖学会全国学術集会
  • Place of Presentation: 長崎