The investigating the molecular mechanisms of cognitive impairment due to cancer chemotherapy and its prevention

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: TANIMUKAI Hitoshi 大阪大学, 大学院・医学系研究科, 特任助教(常勤) (60432481)
• Co-Investigator(Kenkyū-buntansha): KUDO Takashi 大阪大学, 大学院・医学系研究科, 准教授 (10273632) ; MORIHARA Takashi 大阪大学, 大学院・医学系研究科, 助教 (90403196) ; OKAMOTO Yoshiaki 大阪大学, 大学院・薬学研究科, 講師 (90432442) ; TSUGANE Mamiko 大阪大学, 大学院・薬学研究科, 助教 (00469991)
• Project Period (FY): 2009 – 2011
• Keywords: 認知機能障害 / 抗がん剤 / ケモブレイン / 小胞体ストレス / 予防

Research Abstract

To investigate the molecular mechanisms of chemotherapy induced cognitive impairment, we studied the neuronal toxicity(NT) of paclitaxel(Px), fluorouracil(5-FU), and cyclophosphamide(CPA) on neuronal culture cells(SY5Y and SK-N-SH) and further investigated its relationship to endoplasmic reticulum stress(ER stress). Significant NT was observed in cells treated with Px and 5-FU in dose dependent manner, but not with CPA. In addition, the induction of both p-eIF2αand GRP78/ 94 were observed in cells by Px or 5-FU treatment. Pre-treatment of cells with Bip inducer X(BIX) reduced Px-induced NT but not 5-FU induced NT. These data suggest that Px induced NT probably relates to ER stress and BIX could prevent the Px induced NT as including chemobrain.

Research Products

• [Journal Article] ER stress and neuropsychiatric disease (2012)
  • Author(s): Kudo T.
  • Journal Title: ER stress and neuropsychiatric disease Volume: 114(2) Pages: 115-23
  • Peer Reviewed
• [Journal Article] Sigma-1Rs are upregulated via PERK/ eIF2α/ ATF4 pathway and execute protective function in ER stress (2011)
  • Author(s): Mitsuda T, Omi T, Tanimukai H, Sakagami Y, Tagami S, Okochi M, Kudo T, Takeda M.
  • Journal Title: Biochem Biophys Res Commun Volume: Nov 25 ; 415(3) Pages: 519-25
  • Peer Reviewed
• [Journal Article] Molecular chaperone inducer : a possible treatment for Alzheimer disease (2011)
  • Author(s): Kudo T.
  • Journal Title: Rinsho Shinkeigaku Volume: Nov ; 51(11) Pages: 889
  • Peer Reviewed
• [Journal Article] がん疼痛に伴う精神症状の評価とその対策 (2011)
  • Author(s): 谷向仁、壁下康信
  • Journal Title: Progress in Medicine Volume: 31(5) Pages: 1235-1239
• [Presentation] 血液がん患者における不眠の実態及び抑うつとの関連に関する研究 (2011)
  • Author(s): 谷向仁、平井啓、足立祥洋
  • Organizer: 第16回日本緩和医療学会学術大会
  • Place of Presentation: 札幌,日本
  • Year and Date: 2011-07-29
• [Presentation] "A retrospective chart review of agitation in terminal cancer patients (2011)
  • Author(s): Okamoto Y, Nagase M, Tsuneto S, Tanimukai H, Matsuda Y, Okishiro N, Kumakura Y, Ono Y, Tsugane M, Takagi T, Uejima E.
  • Organizer: 12^<th> Congress of the European Association for Palliative Care
  • Place of Presentation: Lisbon Congress Center, Portugal
  • Year and Date: 2011-05-20
• [Presentation] Can Trazodone Improve Insomnia and Nightmare in Cancer Patients?: A Report of Two Cases (2011)
  • Author(s): Tanimukai H, Kumakura Y, Okishiro N, Matsuda Y, Okamoto Y, Kabeshita Y, Ohno Y, Tsuneto S.
  • Organizer: 12^<th> Congress of the European Association for Palliative Care
  • Place of Presentation: Lisbon Congress Center, Portugal
  • Year and Date: 2011-05-19
• [Presentation] がん患者にみられる様々な認知機能障害～せん妄を中心に～ (2010)
  • Author(s): 谷向仁
  • Organizer: 第6回北摂緩和医療懇話会
  • Place of Presentation: 大阪,日本
  • Year and Date: 2010-09-03