Establishment of safe anesthesia methods for dementia patients

• Project/Area Number: 15K10541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagoya City University
• Principal Investigator: SOBUE Kazuya 名古屋市立大学, 大学院医学研究科, 教授 (90264738)
• Co-Investigator(Kenkyū-buntansha): 杉浦 健之 名古屋市立大学, 大学院医学研究科, 准教授 (20295611) ; 浅井 清文 名古屋市立大学, 大学院医学研究科, 教授 (70212462)
• Co-Investigator(Renkei-kenkyūsha): ISHII Fumiyasu 日本福祉大学, 健康科学部, 教授 (90515610) ; YAMAMOTO Naoki 北陸大学, 薬学部, 講師 (90393157)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アルツハイマー型認知症 / 麻酔 / アルツハイマー / 高次脳機能 / 麻酔薬 / 認知症 / 神経細胞 / アストロサイト

Outline of Final Research Achievements

Recently, patients with dementia such as Alzheimer type dementia (AD) are increasing. Anesthesia against AD has a possibility of deteriorating cognitive function after surgery. The pathological future of AD is senile plaque due to aggregation of amyloid β (Aβ) and neurofibrillary tangle (microtubule aggregation, Tau abnormal phosphorylation).
In this study, propofol, barbital and midazolam showed little influence on accumulation of Aβ in cultured neurons and mouse brain, whereas ketamine and haloperidol could be promoted. In addition, as a preventive measure, SKF 10047 which is a σ 1 receptor agonist and epigallocatechin were found to promote Aβ degradation. This research provides a clue to the development of safe anesthesia and preventive measures against AD.

Research Products

• [Journal Article] Epigallocatechin gallate induces extracellular degradation of amyloid β-protein by increasing neprilysin secretion from astrocytes through activation of ERK and PI3K pathways. (2017)
  • Author(s): Yamamoto N, Shibata M, Ishikuro R, Tanida M, Taniguchi Y, Ikeda-Matsuo Y, Sobue K.
  • Journal Title: Neuroscience. Volume: 362 Pages: 70-78
  • DOI: 10.1016/j.neuroscience.2017.08.030
  • Peer Reviewed
• [Journal Article] The σ1 receptor regulates accumulation of GM1 ganglioside-enriched autophagosomes in astrocytes. (2017)
  • Author(s): Kasahara, R., Yamamoto, N., Suzuki, K. and Sobue, K.
  • Journal Title: Neuroscience Volume: 340 Pages: 176-187
  • DOI: 10.1016/j.neuroscience.2016.10.058
  • Peer Reviewed / Open Access
• [Journal Article] Simvastatin and atorvastatin facilitates amyloid β-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways. (2016)
  • Author(s): Yamamoto, N., Fujii, Y., Kasahara, R., Tania, M., Ohora, K., Ono, Y., Suzuki, K. and Sobue, K.
  • Journal Title: Glia Volume: 64 Issue: 6 Pages: 952-962
  • DOI: 10.1002/glia.22974
  • Peer Reviewed
• [Journal Article] dazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor. (2015)
  • Author(s): Yamamoto N, Arima H, Sugiura T, Hirate H, Kusama N, Suzuki K, Sobue K
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Issue: 4 Pages: 547-53
  • DOI: 10.1016/j.bbrc.2015.01.022
  • Peer Reviewed / Open Access
• [Presentation] インスリンによるアストロサイトのネプリライシンとインスリン分解酵素の発現調節の検討 (2018)
  • Author(s): 山本直樹、谷田守、石黒凌、祖父江和哉
  • Organizer: 第36回日本認知症学会学術集会
• [Presentation] 培養アストロサイト発現ネプリライシンとインスリン分解酵素のインスリンによる発現調節の検討 (2017)
  • Author(s): 山本直樹、谷田守、石黒凌、祖父江和哉
  • Organizer: 日本薬学会第138回年会