Functional analysis of the schizophrenia-associated factor DBZ in oligodendrocytes

• Project/Area Number: 15K18381
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kindai University
• Principal Investigator: SHIMIZU Shoko 近畿大学, 東洋医学研究所, 助教 (50572731)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: オリゴデンドロサイト / 統合失調症 / DISC1 / DBZ / ミエリン / ミエリン形成

Outline of Final Research Achievements

Recent studies have implicated oligodendrocyte (OL) abnormalities in schizophrenia. To better elucidate the molecular mechanisms underlying the pathophysiology of schizophrenia, we investigated the function of DISC1-Binding Zinc finger protein (DBZ) in OL differentiation as DISC1 is a risk gene of schizophrenia. We examined the dynein cofactor, nuclear distribution E homolog 1 (NDE1), which binds to DBZ in OLs. Postnatally, when myelin formation is active, NDE1 mRNA is expressed in OL lineage cells in the mouse corpus callosum. An in vitro analysis revealed that NDE1 knockdown impaired OL differentiation. In addition, overexpression of the dynein-binding region of NDE1 resulted in impairments in OL differentiation like those observed following NDE1 knockdown. These results suggested that the DBZ-NDE1-dynein complex regulates OL differentiation.

Research Products

• [Journal Article] Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression. (2016)
  • Author(s): Miyata S, Taniguchi M, Koyama Y, Shimizu S, Tanaka T, Yasuno F, Yamamoto A, Iida H, Kudo T, Katayama T, Tohyama M.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 23084-23084
  • DOI: 10.1038/srep23084
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sgk1 regulates desmoglein 1 expression levels in oligodendrocytes in the mouse corpus callosum after chronic stress exposure. (2015)
  • Author(s): Miyata S, Yoshikawa K, Taniguchi M, Ishikawa T, Tanaka T, Shimizu S, Tohyama M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 464(1) Issue: 1 Pages: 76-82
  • DOI: 10.1016/j.bbrc.2015.05.109
  • Peer Reviewed
• [Presentation] オリゴデンドロサイト分化におけるDBZの機能解析 (2017)
  • Author(s): 清水 尚子
  • Organizer: 第40回日本神経科学大会
• [Presentation] Functional analysis of DISC1-binding zinc finger protein (DBZ) during oligodendrocyte differentiation (2016)
  • Author(s): 清水尚子、遠山正彌、宮田信吾
  • Organizer: 第21回グリア研究会
  • Place of Presentation: 千里ライフサイエンスセンター (豊中市）
  • Year and Date: 2016-12-03
• [Presentation] オリゴデンドロサイトにおける統合失調症関連因子の機能解析 (2016)
  • Author(s): 清水尚子、遠山正彌、宮田信吾
  • Organizer: 第92回日本解剖学会近畿支部学術集会
  • Place of Presentation: 近畿大学(東大阪市）
  • Year and Date: 2016-11-27
• [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation (2016)
  • Author(s): 清水尚子、田中貴士、遠山正彌、宮田信吾
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
  • Place of Presentation: 福岡国際会議場 (福岡市）
  • Year and Date: 2016-09-08
• [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation (2016)
  • Author(s): S Shimizu, S Miyata, T Tanaka, M Tohyama
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜 (横浜市）
  • Year and Date: 2016-07-20
• [Presentation] うつ病発症に関わるオリゴデンドロサイトの機能異常に関する研究 (2015)
  • Author(s): 宮田信吾、清水尚子、田中貴士、松村彬世、川上あゆみ、鹿島美恵子、遠山正彌
  • Organizer: BMB2015, 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] DBZ, a CNS-specific DISC1 binding protein, positively regulates oligodendrocyte differentiation (2015)
  • Author(s): Shoko Shimizu, Shingo Miyata, Takashi Tanaka, Masaya Tohyama
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2015-09-11