Molecular mechanisms of the DISC1 functions in astrocyte-a study that is focused on the relationship with schizophrenia-

• Project/Area Number: 15K06790
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kindai University
• Principal Investigator: TOHYAMA Masaya 近畿大学, 東洋医学研究所, 教授 (40028593)
• Co-Investigator(Kenkyū-buntansha): 田中 貴士 近畿大学, 付置研究所, 助教 (30734694) ; 清水 尚子 近畿大学, 東洋医学研究所, 助教 (50572731) ; 宮田 信吾 近畿大学, 東洋医学研究所, 教授 (70403194)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DISC1 / アストロサイト / 統合失調症 / 分化

Outline of Final Research Achievements

The major psychiatric disorders such as schizophrenia are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of schizophrenia remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1) might cause major psychiatric disorders such as schizophrenia. In our previous study, we observed that DISC1 expression detected in primary astrocytes cultures.
In this study, we further identified that DISC1 expressions were observed in both fibrillary astrocyte and radial astrocyte in the mice brain. Our data suggest that DISC1 in astrocyte might be possibly related to schizophrenia.

Research Products

• [Journal Article] The antistress effect of the Kampo medicine Yokukansan. (2017)
  • Author(s): Shimizu S, Tohyama M, Miyata S.
  • Journal Title: The Autonomic Nervous System Volume: 54 Pages: 21-25
  • Peer Reviewed
• [Journal Article] BPSDに対する抑肝散のメカニズム (2017)
  • Author(s): 遠山正彌、島田昌一
  • Journal Title: Science of Kampo Medicine 漢方医学 Volume: 41 Pages: 26-29
  • Peer Reviewed
• [Journal Article] ミトコンドリアタンパク質TRAP1機能と ミトコンドリアダイナミクス -脳機能との関わり (2016)
  • Author(s): 高村明孝、宮田信吾、遠山正彌、片山泰一
  • Journal Title: 脳21 Volume: 19 Pages: 230-237
• [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
• [Journal Article] Alterations in dendrite and spine morphology of cortical pyramidal neurons in DISC1-binding zinc finger protein (DBZ) knockout mice. (2015)
  • Author(s): Koyama Y, Hattori T, Nishida T, Hori O, Tohyama M.
  • Journal Title: Front Neuroanat. Volume: 30 Pages: 9-52
  • DOI: 10.3389/fnana.2015.00052
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Physiological ER Stress Mediates the Differentiation of Fibroblasts. (2015)
  • Author(s): Matsuzaki S, Hiratsuka T, Taniguchi M, Shingaki K, Kubo T, Kiya K, Fujiwara T, Kanazawa S, Kanematsu R, Maeda T, Takamura H, Yamada K, Miyoshi K, Hosokawa K, Tohyama M, Katayama T.
  • Journal Title: PLoS One. Volume: 10(4) Issue: 4 Pages: e0123578-e0123578
  • DOI: 10.1371/journal.pone.0123578
  • Peer Reviewed / Open Access
• [Journal Article] Disturbance of oligodendrocyte function plays a key role in the pathogenesis of schizophrenia and major depressive disorder. (2015)
  • Author(s): Miyata S, Hattori T, Shimizu S, Ito A, Tohyama M
  • Journal Title: Biomed Res. Int Volume: 2015 Pages: 492367-492367
  • DOI: 10.1155/2015/492367
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation. (2015)
  • Author(s): 1.Okamoto, M., Iguchi, T., Hattori, T., Matsuzaki, S., Koyama, Y., Taniguchi, M., Kodama, M., Xie, M-J., Yagi, H., Shimizu, S., Konishi, Y., Yoshimi, T., Tachibana, T., Fujieda, S., Katayama, T., Ito, A., Hirotsune, S., Tohyaman, M. and Sato, M.
  • Journal Title: J Neurosci Volume: 18 Issue: 7 Pages: 2942-2958
  • DOI: 10.1523/jneurosci.5029-13.2015
  • Peer Reviewed / Open Access
• [Journal Article] Molecular basis of major psychiatric diseases such as schizophrenia and depression. (2015)
  • Author(s): Tohyama M, Miyata S, Hattori T, Shimizu S, Matsuzaki S.
  • Journal Title: Anat Sci Int. Volume: 90(3) Issue: 3 Pages: 137-43
  • DOI: 10.1007/s12565-014-0269-3
  • Peer Reviewed
• [Presentation] うつ病性障害発症とオリゴデンドロサイト機能 (2017)
  • Author(s): 宮田信吾、清水尚子、松村彬世、川上あゆみ、鹿島美恵子、遠山正彌
  • Organizer: 第122回日本解剖学会総会・全国学術総会
  • Place of Presentation: 長崎 長崎大学
  • Year and Date: 2017-03-28
• [Presentation] うつ病発症における脳白質構造変化とオリゴデンドロサイト機能変化の関連 (2017)
  • Author(s): Miyata S, Shimizu S, Ishino Y, Yamamoto A, Kawakami A, Tohyama M
  • Organizer: 2017年度生命科学系学会合同年次大会(ComBio2017)
• [Presentation] Molecular mechanisms of the onset of neuropsychiatric disorders by the changes in glial functions (2017)
  • Author(s): Miyata S, Shimizu S, Ishino Y, Tohyama M
  • Organizer: The 60th Annual Meeting of the Japanese Society for Neurochemistry
• [Presentation] Functional analysis of DISC1 binding protein DBZ in oligodendrocyte differentiation (2017)
  • Author(s): Shimizu S, Miyata S, Tohyama M
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
• [Presentation] The cadherin superfamily proteins in oligodendrocytes in the mouse corpus callosum were changed after chronic stress exposure (2017)
  • Author(s): Miyata S, Shimizu S, Yamamoto A, Kawakami A, Tohyama M
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
• [Presentation] 慢性ストレスによる脳白質機能変化と大うつ病性障害の関連 (2017)
  • Author(s): Miyata S, Shimizu S, Yamamoto A, Kawakami A, Tohyama M
  • Organizer: 第17回日本抗加齢医学会総会
• [Presentation] microRNAを介した脳内ストレス応答機構への抑肝散の効果 (2016)
  • Author(s): 宮田信吾、清水尚子、松村彬世、川上あゆみ、遠山正彌
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Association between stress-induced Ranvier nodes structural abnormalities and reduced oligodendrocyte activity in major depressive disorder (2016)
  • Author(s): S. Miyata, S. Shimizu, T. Tanaka, M. Tohyama.
  • Organizer: Neuroscience 2016, SfN's 46th annual meeting
  • Place of Presentation: 米国 San Diego Convention Center
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] うつ病発症に関わる脳白質オリゴデンドロサイトの機能変化 (2016)
  • Author(s): 宮田信吾、清水尚子、田中貴士、松村彬世、川上あゆみ、遠山正彌
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台 仙台国際センター
  • Year and Date: 2016-09-25
• [Presentation] 精神疾患関連分子によるオリゴデンドロサイト発達制御 (2016)
  • Author(s): 宮田信吾、清水尚子、服部剛志、遠山正彌
  • 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 福岡国際会議場
  • Year and Date: 2016-09-08
• [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 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] Overexpression of MARCKSL1 induces anxiety-like behavior via hyperactivation of the basolateral amygdala (2016)
  • Author(s): 田中貴士、清水尚子、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 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] Structural alterations and functional declines of the nodes of Ranvier by exposed repeated stressful events is associated with the onset of major depressive disorder (2016)
  • Author(s): S Miyata, S Shimizu, T Tanaka, A Matsumura, A Kawakami, M Tohyama.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-07-20
• [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: 横浜 パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] MARCKS-like 1 protein is associated with the pathogenesis of anxiety and depressive disorders (2016)
  • Author(s): T Tanaka, S Miyata, S Shimizu, M Tohyama.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] PRMT1-dependent arginine methylation on hnRNP K regulates dendritic transport of alpha CaMKII mRNA (2016)
  • Author(s): Y Mori, T Iguchi, S Miyata, M Tohyama, M Sato.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] The Kampo medicine Yokukansan normalizes glucocorticoid receptor protein expression in the mice brain by regulating microRNA expressions after stress exposure (2016)
  • Author(s): S Miyata, S Shimizu, T Tanaka, M Tohyama.
  • Organizer: RNA 2016, The RNA Society of Japan 18th Annual Meeting AND The 21st Annual Meeting of the RNA Society,
  • Place of Presentation: 京都 国際会議場
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [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: 大阪 千里ライフサイエンスセンター
• [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: 大阪 近畿大学
• [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: 埼玉 大宮ソニックシティ
  • Year and Date: 2015-09-11
• [Presentation] A novel approach for visualizing spatiotemporal regulation of cell-wide or localized translation (2015)
  • Author(s): Shingo Miyata, Shoko Shimizu, Takashi Tanaka, Yasutake Mori, Masaya Tohyama
  • Organizer: 新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」 第 2 回夏の(国際)ワークショッフ
  • Place of Presentation: 岡崎 生理学研究所
  • Year and Date: 2015-07-10
  • Int'l Joint Research
• [Presentation] Double nicking by CRISPR/Cas9 enhances genome editing specificity (2015)
  • Author(s): Takashi Tanaka, Shoko Shimizu, Masaya Tohyama, Shingo Miyata
  • Organizer: 新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」 第 2 回夏の(国際)ワークショッフ
  • Place of Presentation: 岡崎 生理学研究所
  • Year and Date: 2015-07-10
  • Int'l Joint Research
• [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)
  • URL: http://www.med.kindai.ac.jp/toyo/study/index.html
• [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門(基礎研究部門)研究成果
  • URL: http://www.med.kindai.ac.jp/toyo/study/results.html
• [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門（基礎研究部門）
  • URL: http://www.med.kindai.ac.jp/toyo/study/index.html
• [Remarks] 近畿大学 東洋医学研究所 分子脳科学研究部門（基礎研究部門）研究成果
  • URL: http://www.med.kindai.ac.jp/toyo/study/results.html