Research into the causes and treatment of olfactory hypersensitivity

• Project/Area Number: 18K19617
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Shimada Shoichi 大阪大学, 医学系研究科, 教授 (20216063)
• Co-Investigator(Kenkyū-buntansha): 近藤 誠 大阪大学, 医学系研究科, 准教授 (50633012) ; 中村 雪子 大阪大学, 医学系研究科, 助教 (90548083) ; 小山 佳久 大阪大学, 医学系研究科, 助教 (40397667)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 嗅覚過敏 / 嫌悪学習 / 嗅覚 / 外傷後ストレス障害 / PTSD / 恐怖記憶 / 5-HT3受容体

Outline of Final Research Achievements

Hyperosmia is one of the olfactory disorders. When mice encounter a situation that is harmful and dangerous, the surrounding odor and its negative experience are conditioned. In order to avoid the situation quickly, the mice become more sensitive to the odor and show an aversive reaction to the odor. In order to study hyperosmia, we attempted to establish a method for creating a reliable model of olfactory hypersensitivity and try to develop a therapeutic drug. When mice drink a trace amount of odor substance, the mice sense a trace amount of odor molecules that volatilize in the oral cavity. We have developed a hyperosmia/aversive conditioning model using these mice with intraperitoneal injection of LiCl.

Academic Significance and Societal Importance of the Research Achievements

家、学校、職場などの建物では、普段あまり感じられないような微弱な固有のにおいが存在する。学校や職場でいじめやハラスメントなどトラウマになるような体験をすると、ヒトは無意識のうちに、その建物のにおいのする場所でつらい思いをするというような条件づけが起こり、学校や職場の建物に近づき、そのにおいを感じると、咳嗽、動悸、過呼吸、めまい、頭痛などの自律神経症状や不定愁訴が現れ、嗅覚過敏の症状が発症する場合がある。また最終的に登校拒否、出勤拒否、引きこもりなどの原因にも繋がると考えられる。本研究では、これらの嗅覚過敏モデル動物の作製方法を確立し、 治療法の開発につなげることを目指す。

Research Products

• [Journal Article] Renoprotective and neuroprotective effects of enteric hydrogen generation from Si-based agent. (2020)
  • Author(s): Kobayashi Y, Imamura R, Koyama Y, Kondo M, Kobayashi H, Nonomura N, Shimada S.
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 5859-5859
  • DOI: 10.1038/s41598-020-62755-9
  • Peer Reviewed / Open Access
• [Journal Article] Yokukansan-induced reduction of ethanol preference is associated with antagonism of 5-HT3 receptors. (2019)
  • Author(s): Nakamura Y, Kondo M, Koyama Y, Shimada S.
  • Journal Title: Phytomedicine Volume: 59 Pages: 152897-152897
  • DOI: 10.1016/j.phymed.2019.152897
  • Peer Reviewed
• [Journal Article] Rat model of Meniere’s attack: intratympanic injection of potassium chloride produces direction-changing spontaneous nystagmus and hearing fluctuations. (2019)
  • Author(s): Kamakura T, Kitahara T, Kondo M, Horii A, Hanada Y, Takimoto Y, Ishida Y, Nakamura Y, Imai T, Inohara H, Shimada S.
  • Journal Title: Audiology and Neurotology Volume: 24 Issue: 5 Pages: 217-223
  • DOI: 10.1159/000502275
  • Peer Reviewed
• [Journal Article] Expression Analysis of Serotonin Receptors, Serotonin Transporter and l-Amino Acid Decarboxylase in the Mouse Sphenopalatine Ganglion by RT-PCR, Northern Blot Analysis and In Situ Hybridization. (2019)
  • Author(s): Y. Ishida, Y. Sugiura, T. Magome, T. Kamakura, Y. Takimoto, Y.Hanada, K.Kitayama, Y. Nakamura, S. Shimada, N. Ohta, R. Naono-Nakayama, K. Kamijo
  • Journal Title: Neuroscience Volume: 411 Pages: 23-36
  • DOI: 10.1016/j.neuroscience.2019.05.028
  • Peer Reviewed
• [Journal Article] SR 57227A is a partial agonist/partial antagonist of 5-HT3 receptor and inhibits subsequent 5-HT- or SR 57227A-induced 5-HT3 receptor current. (2019)
  • Author(s): Nakamura Y, Kondo M, Koyama Y, Shimada S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 508 Issue: 2 Pages: 590-596
  • DOI: 10.1016/j.bbrc.2018.11.174
  • Peer Reviewed
• [Journal Article] Yokukansan contains compounds that antagonize the 5-HT3 receptor. (2018)
  • Author(s): Nakamura Y, Ishida Y, Kondo M, Shimada S
  • Journal Title: Phytomedicine Volume: 43 Pages: 120-125
  • DOI: 10.1016/j.phymed.2018.04.034
  • Peer Reviewed
• [Presentation] 5-HT3受容体を介する新たな抗うつメカニズム (2019)
  • Author(s): 近藤誠、小山佳久、中村雪子、臼井紀好、島田昌一
  • Organizer: 第１２４回日本解剖学会総会全国学術集会
• [Presentation] The significance of complete distributional analysis of the 5-HT3A receptor (2018)
  • Author(s): Koyama Y, kondo M, Shimada S
  • Organizer: 第６１回日本神経化学会大会
• [Presentation] A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects (2018)
  • Author(s): Kondo M, Koyama Y, Nakamura Y, Usui N, Shimada S
  • Organizer: 第６１回日本神経化学会大会