Elucidation of the mechanisms by which neurogenesis is impaired in dyslipidemic patients

• Project/Area Number: 26350921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: National Defense Medical College
• Principal Investigator: Ishizuka Toshiaki 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 医学教育部医学科専門課程, 教授 (30399117)
• Co-Investigator(Kenkyū-buntansha): 鈴木 豪 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 薬理学, 講師 (50649035) ; 渡辺 康裕 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 薬理学, 名誉教授 (90127324)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経前駆細胞 / 神経分化 / 酸化LDL / LOX-1 / PKC / Ａｋｔリン酸化 / CREBリン酸化 / Aktリン酸化 / 神経幹細胞 / 酸化LDL受容体

Outline of Final Research Achievements

We revealed that stimulation with oxidized LDL (ox-LDL) significantly suppressed the differentiation of mouse neural progenitor cells into neural cells. In addition, it was found that the effects of ox-LDL is due to the activation of LOX-1 which activates PKC and inhibits the phosphorylation of Akt and CREB. Thus, the modulation of LOX-1 may ameliorate the impaired neurogenesis and neuropsychiatric function in dyslipidemic patients.

Research Products

• [Journal Article] Tumor growth limited to subcutaneous site vs tumor growth in (2017)
  • Author(s): Masuda J, Takayama E, Strober W, Satoh A, Morimoto Y, Honjyo Y, Ichinose T, Tokuno S, Ishizuka T, et al.
  • Journal Title: Oncology Reports Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 幹細胞機能に影響を及ぼす細胞内機能の解明と再生医療への応用 (2016)
  • Author(s): 石塚 俊晶
  • Journal Title: 防衛医科大学校雑誌 Volume: 41 Pages: 47-47
• [Journal Article] Diagnostic performance of measuring antibodies to the glycopeptidolipid core antigen specific to Mycobacterium avium complex in patients with rheumatoid arthritis: results from a cross-sectional observational study (2015)
  • Author(s): Hirose W, Uchiyama T, Nemoto A, Harigai M, Itoh K, Ishizuka T, Matsumoto M, Yamaoka K, Nanki T
  • Journal Title: Arthritis Research and Therapy Volume: 17 Issue: 1 Pages: 273-273
  • DOI: 10.1186/s13075-015-0787-y
  • Peer Reviewed / Open Access
• [Journal Article] Stimulation of 5-hydroxytryptamine 4 receptor enhnaces differentiation of mouse induced pluripotent stem cells into neural progenitor cells. (2014)
  • Author(s): T. Ishizuka, H. Goshima, A. Ozawa, Y. Watanabe
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 41 Issue: 5 Pages: 345-350
  • DOI: 10.1111/1440-1681.12224
  • Peer Reviewed
• [Journal Article] Involvement of beta-adrenoceptors in the differentiation of human induced pluripotent stem cells into mesodermal progenitor cells. (2014)
  • Author(s): Ishizuka T, Goshima H, Ozawa A, Watanabe Y.
  • Journal Title: Eur J Pharmacol Volume: 740 Pages: 28-34
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 多能性幹細胞の機能調節に関わる細胞膜受容体 (2014)
  • Author(s): 石塚 俊晶、渡辺 康裕
  • Journal Title: 日本薬理学雑誌 Volume: 144 Pages: 13-16
  • NAID: 130004437199
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 脂質異常症における神経新生障害の機序解明：酸化ＬＤＬ刺激は神経前駆細胞の分化を抑制する (2017)
  • Author(s): 石塚 俊晶、佐藤 泰司、野村 さやか、小澤 亜也子、勝浦 美枝子
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] 代謝性疾患治療を指向したＬＸＲbeta選択的なアゴニストの創製 (2017)
  • Author(s): 野村 さやか、梅田 香織、石塚 俊晶、槇島 誠、橋本 祐一、石川 稔
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] 小児への麻酔曝露が自閉症発症リスクへ与える影響 (2017)
  • Author(s): 嶋田 哲也、佐藤 泰司、神尾 陽子、中村 好宏、中島 宏、赤井 亮介、湯舟 晋也、風間 富栄、石塚 俊晶
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] アデノシン分解酵素の神経保護作用 (2017)
  • Author(s): 太田 宏之、田村 吏沙、佐藤 泰司、丹生谷 正史、野々山 恵章、石塚 俊晶、西田 育弘
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] BK channel activation at spinal microglia is important for the induction of neuropathic pain in mice. (2016)
  • Author(s): Morohashi T, Itakura S, Hayashi Y, Kawaguchi Y, Nakanishi H, Nakata T, Ishizuka T, Meredith AL, Satoh Y.
  • Organizer: 16 th World Congress on Pain
  • Place of Presentation: Yokohama
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Roles of extracellular signal-regulated protein kinase 2 (ERK2) in the peripheral nervous system for the mechanism of pain transmission. (2016)
  • Author(s): Itakura S, Morohashi T, Otsubo Y, Endo S, Satoh T, Wood JN, Ishizuka T, Satoh Y.
  • Organizer: 16th World Congress of Pain
  • Place of Presentation: Yokohama
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Involvement of G-coupled receptor-dependent cyclic AMP/PKA siganling pathway on neural differentiation of mouse iPS cells. (2016)
  • Author(s): Ishizuka T, Ozawa A, Katsuura M, Satoh Y.
  • Organizer: ISSCR 2016
  • Place of Presentation: San Francisco
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Effects of Wnt3a, TNFalpha, or nicotine on differentiation of human intestinal stem cells into intestinal epithelial cells (2016)
  • Author(s): Ishizuka T, Ozawa A, Katsuura M, Satoh Y.
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] 発達期の神経発達における細胞外情報伝達制御キナーゼ(ERK)の役割 (2016)
  • Author(s): 佐藤泰司、湯舟晋也、遠藤昌吾、風間富栄、石塚俊晶
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] Effects of TNF-alpha and nicotine on differentiation of human endodermal progenitor cells into intestinal epithelial cells (2015)
  • Author(s): Ishizuka T, Ozawa A, Sado A, Arata M, Watanabe Y.
  • Organizer: International Society for Stem Cell Research 2015 Annual Meeting
  • Place of Presentation: Stockholm, SWEDEN
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] マウス人工多能性幹細胞の神経前駆細胞への分化におけるG蛋白質共役型受容体を介したcAMP/PKAシグナル伝達系の役割 (2015)
  • Author(s): 石塚 俊晶、小澤 亜也子、新田 宗光、渡辺 康裕
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-19
• [Presentation] Involvement of cannabinoid receptors or muscarinic acetylcholine receptors on differentiation into neural progenitor cells in mouse induced pluripotent stem cells. (2014)
  • Author(s): Ishizuka T, Ozawa A, Arata M, Watanabe Y.
  • Organizer: 43th Annual Meeting of Society for Neuroscinece
  • Place of Presentation: アメリカ、ワシントン
  • Year and Date: 2014-11-19
• [Presentation] ムスカリン型アセチルコリン受容体刺激は、cAMP/PKAシグナル伝達系を阻害してマウス人工多能性幹細胞の神経前駆細胞への分化を抑制する (2014)
  • Author(s): 石塚 俊晶、小澤 亜也子、新田 宗光、渡辺 康裕
  • Organizer: 第131回日本薬理学会関東部会
  • Place of Presentation: 横浜市立大学医学部
  • Year and Date: 2014-10-11
• [Presentation] マウス人工多能性幹細胞の増殖および神経前駆細胞への分化に対するムスカリン型アセチルコリン受容体の関与 (2014)
  • Author(s): 石塚 俊晶、小澤 亜也子、新田 宗光、渡辺 康裕
  • Organizer: 第57回日本神経化学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29
• [Presentation] The stimulation of muscarinic acetylcholine receptors inhibits differentiation of mouse induced pluripotent stem cells into neural progenitor cells. (2014)
  • Author(s): Watanabe Y, Ishizuka T, Ozawa A, Arata M.
  • Organizer: 16th Congress of European Neuroendocrine Association
  • Place of Presentation: ブルガリア
  • Year and Date: 2014-09-12
• [Presentation] Stimualtion with beta-adrenoceptors enhances differentiation of human induced pluripotent stem cells into cardiovascular progenitor cells via PKA-dependent p38 MAPK activation. (2014)
  • Author(s): Watanabe Y, Ishizuka T, Ozawa A, Arata M.
  • Organizer: 17th World Congress of Basic and Clinical Pharmacology
  • Place of Presentation: 南アフリカ共和国
  • Year and Date: 2014-07-13
• [Presentation] マウス人工多能性幹細胞の内胚葉系前駆細胞および肝細胞への分化に対するニコチンの影響 (2014)
  • Author(s): 石塚 俊晶、小澤 亜也子、新田 宗光、渡辺 康裕
  • Organizer: 第130回日本薬理学会関東部会
  • Place of Presentation: 東京、星薬科大学
  • Year and Date: 2014-07-05
• [Presentation] Involvement of 5-HT4 receptor or cannabinoid receptors on differentiation of mouse induced pluripotent stem cells into neural progenitor cells. (2014)
  • Author(s): Ishizuka T, Ozawa A, Arata M, Watanabe Y.
  • Organizer: 12th Annual Meeting of International Society for Stem Cell Research
  • Place of Presentation: カナダ、バンクーバー
  • Year and Date: 2014-06-18
• [Book] Regulation of Signal Transduction in Human Cell Research: Role of the receptor-mediated signaling pathways on the proliferation and differentiation of pluripotent stem cells (2017)
  • Author(s): Ishizuka T
  • Publisher: Springer-Nature