Molecular mechanisms and roles of mitochondrial dynamics in development and diseases of myelinated axons

• Project/Area Number: 26860129
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: University of Yamanashi
• Principal Investigator: OHNO Nobuhiko 山梨大学, 総合研究部, 准教授 (10432155)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Mitochondria / Myelination / Demyelination / Electron microscopy / Conductive resin / 軸索 / ミトコンドリア / 脱髄 / 髄鞘

Outline of Final Research Achievements

We demonstrated alterations of mitochondrial distribution and dynamics during development of mouse central nervous system. In addition, changes of mitochondrial dynamics were caused specifically in demyelinated segments in the mouse dysmyelination model. In the 3D ultrastructural analyses using scanning electron microscopy, improvement of tissue preparation procedures and development of conductive resins were explored to achieve patent application. The carbon based conductive resin could reduce charging and improve imaging in the 3D ultrastructural analyses. The obtained results were published as several papers and presented in conferences.

Research Products

• [Int'l Joint Research] クリーブランドクリニック(米国)
• [Journal Article] Conductive resins improve charging and resolution of acquired images in electron microscopic volume imaging. (2016)
  • Author(s): Nguyen HB, Thai TQ, Saitoh S, Wu B, Saitoh Y, Shimo S, Fujitani H, Otobe H, Ohno N.
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 23721-23721
  • DOI: 10.1038/srep23721
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy (2016)
  • Author(s): Thai TQ, Nguyen HB, Saitoh S, Wu B, Saitoh Y, Shimo S, Elewa YH, Ichii O, Kon Y, Takaki T, Joh K, Ohno N.
  • Journal Title: Med Mol Morphol Volume: Epub ahead of print Issue: 3 Pages: 1-9
  • DOI: 10.1007/s00795-016-0134-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recent advancement in the challenges to connectomics. (2016)
  • Author(s): Ohno N, Katoh M, Saitoh Y, Saitoh S.
  • Journal Title: Microscopy Volume: 65 Issue: 2 Pages: 97-107
  • DOI: 10.1093/jmicro/dfv371
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Involvement of membrane skeletal molecules in the Schmidt-Lanterman incisure in Schwann cells. (2016)
  • Author(s): Terada N, Saitoh Y, Kamijo A, Ohno S, Ohno N.
  • Journal Title: Med Mol Morphol Volume: - Issue: 1 Pages: 5-10
  • DOI: 10.1007/s00795-015-0125-0
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] SSSEM による脳組織の3 次元再構築 (2016)
  • Author(s): 大野伸彦
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 368-369
• [Journal Article] Mitochondrial fission augments capsaicin-induced axonal degeneration (2015)
  • Author(s): Hao Chiang, Nobuhiko Ohno, Yu-Lin Hsieh, Don J. Mahad, Shin Kikuchi, Hitoshi Komuro, Sung-Tsang Hsieh, Bruce D. Trapp
  • Journal Title: Acta Neuropathol. Volume: 129 Issue: 1 Pages: 81-96
  • DOI: 10.1007/s00401-014-1354-3
  • Peer Reviewed
• [Journal Article] Three-dimensional volume imaging with electron microscopy toward connectome (2015)
  • Author(s): Nobuhiko Ohno, Mitsuhiko Katoh, Yurika Saitoh, Sei Saitoh, Shinichi Ohno
  • Journal Title: Microscopy Volume: 64 Issue: 1 Pages: 17-26
  • DOI: 10.1093/jmicro/dfu112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons (2014)
  • Author(s): Nobuhiko Ohno, Hao Chiang, Don J. Mahad, Grahame J. Kidd, LiPing Liu, Richard M. Ransohoff, Zu-Hang Sheng, Hitoshi Komuro, Bruce D. Trapp
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Issue: 27 Pages: 9953-9958
  • DOI: 10.1073/pnas.1401155111
  • Peer Reviewed
• [Journal Article] Differential roles of microglia and monocytes in the inflamed central nervous system (2014)
  • Author(s): Ryo Yamasaki, Haiyan Lu, Oleg Butovsky, Nobuhiko Ohno, Anna M. Rietsch, Ron Cialic, Pauline M. Wu, Camille E. Doykan, Jessica Lin, Anne C. Cotleur, Grahame Kidd, Musab M. Zorlu, Nathan Sun, Weiwei Hu, LiPing Liu, Jar-Chi Lee, Sarah E. Taylor, Lindsey Uehlein, Debra Dixon, Jinyu Gu, Crina M. Floruta, Min Zhu, et al.
  • Journal Title: J Exp Med. Volume: 211 Issue: 8 Pages: 1533-1549
  • DOI: 10.1084/jem.20132477
  • Peer Reviewed
• [Journal Article] SBF-SEMによる生体内3次元微細構造観察の試料作製とその応用 (2014)
  • Author(s): 大野伸彦、齊藤成、齊藤百合花、大野伸一
  • Journal Title: 顕微鏡 Volume: 49 Pages: 166-170
  • NAID: 130007701728
  • Peer Reviewed
• [Presentation] 試料作製法の進歩が拓くSEM連続断面観察法の展望 (2016)
  • Author(s): 大野伸彦
  • Organizer: 第121回日本解剖学会総会
  • Place of Presentation: ビッグパレット福島(福島県郡山市)
  • Year and Date: 2016-03-28
• [Presentation] Development of conductive resin to facilitate 3D ultrastructural imaging in life science (2015)
  • Author(s): Ohno N, Otobe H, Fujitani H
  • Organizer: The 2nd East-Asia Microscopy Conference Young Scientists Satellite Meeting
  • Place of Presentation: 淡路夢舞台(兵庫県淡路市)
  • Year and Date: 2015-11-27
  • Int'l Joint Research / Invited
• [Presentation] SEM断面観察法をより簡便にする試料作製法の進歩 (2015)
  • Author(s): 大野伸彦、乙部博英、藤谷洋
  • Organizer: 日本臨床分子形態学会
  • Place of Presentation: 長崎大学(長崎県長崎市)
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] Mitochondrial fission and elongation in microglia induced by activation with LPS (2015)
  • Author(s): Katoh M, Wu B, Nguyen HB, Thai TQ, Sakoh T, Saitoh Y, Saitoh S, Shinozaki Y, Koizumi S, Ohno N
  • Organizer: 日本神経化学会
  • Place of Presentation: 大宮ソニックシティ(埼玉県さいたま市)
  • Year and Date: 2015-09-11
• [Presentation] 有髄神経における神経活動依存性のミトコンドリア動態 (2015)
  • Author(s): 大野伸彦
  • Organizer: 第120回 日本解剖学会総会･全国学術集会
  • Place of Presentation: 神戸国際会議場・展示場（兵庫県）
  • Year and Date: 2015-03-23
  • Invited
• [Presentation] SBF-SEMの応用による疾病モデルおよびヒト組織の3次元微細構造観察 (2014)
  • Author(s): 大野伸彦、齊藤成 、齊藤百合花 、井上朋大 、加藤良平 、大野伸一
  • Organizer: 第46回日本臨床分子形態学会総会・学術集会
  • Place of Presentation: TKP市ヶ谷カンファレンスセンター（東京都）
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] 末梢神経軸索障害におけるミトコンドリア動態の役割 (2014)
  • Author(s): 大野伸彦
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
  • Place of Presentation: 奈良県文化会館、奈良県新公会堂（奈良県）
  • Year and Date: 2014-09-29
  • Invited
• [Presentation] 髄鞘の異常におけるオルガネラ動態の変化 (2014)
  • Author(s): 大野伸彦
  • Organizer: 第55回日本組織細胞化学会総会・学術集会
  • Place of Presentation: 松本市中央公民館（長野県）
  • Year and Date: 2014-09-28
  • Invited
• [Presentation] SBF-SEMを用いた3次元微細構造観察のターゲットと試料作製 (2014)
  • Author(s): 大野伸彦
  • Organizer: 日本顕微鏡学会第70回記念学術講演会
  • Place of Presentation: 幕張メッセ 国際会議場（千葉県）
  • Year and Date: 2014-05-11
  • Invited
• [Remarks] 研究内容、研究成果
  • URL: https://researchmap.jp/ohnoccf/
• [Remarks] 山梨大学研究者総覧 大野伸彦
  • URL: http://erdb.yamanashi.ac.jp/rdb/A_DispInfo.Scholar/3_50/060A2806DABF78C2.html
• [Remarks] 解剖分子組織学教室 ホームページ
  • URL: http://www.med.yamanashi.ac.jp/basic/anat01/
• [Patent(Industrial Property Rights)] 形態観察用試料の調整方法及びそれに用いる液体処理用器具、試料台. (2015)
  • Inventor(s): 大野 伸彦, 乙部 博英, 藤谷 洋
  • Industrial Property Rights Holder: 大野 伸彦, 乙部 博英, 藤谷 洋
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-177235
  • Filing Date: 2015-09-09