Mechanisms of tripartite synaptic transmission

• Project/Area Number: 15H04892
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Mie University
• Principal Investigator: Okada Motohiro 三重大学, 医学系研究科, 教授 (10281916)
• Co-Investigator(Kenkyū-buntansha): 大野 行弘 大阪薬科大学, 薬学部, 教授 (00432534) ; 植田 勇人 三重大学, 医学系研究科, 客員教授 (70244192) ; 杉浦 嘉泰 福島県立医科大学, 医学部, 准教授 (00315665)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: アストロサイト / 三者間伝達 / 統合失調症 / てんかん / 認知症 / ADHD / 機能性疾患 / グリア / 開口分泌

Outline of Final Research Achievements

To explore the novel pathogenesis and pathophysiology of epilepsy, schizophrenia, attention-deficit hyperactivity disorder (ADHD) and dementia, the present study determined the functional abnormalities of tripartite synaptic transmission using in vivo microdialysis and primary cultured astrocytes. The results of this study suggest that the enhancement of astroglial glutamate/cystine antiporter and metabotropic glutamate receptor contribute to the pathophysiology of epilepsy, schizophrenia, ADHD and dementia.

Academic Significance and Societal Importance of the Research Achievements

統合失調症、注意欠陥多動性障害、認知症、てんかんの病態生理に、従来、明らかにされてきた神経伝達機能だけではなく、新たにアストロサイトが非電気的な情報伝達を担っていることを明らかにした。この神経とアストロサイトによる三者間情報伝達の機能補正は、新たな治療法の開発に寄与する。加えて、視床皮質路における三者間情報伝達の認知機能における重要性も同定した

Research Products

• [Journal Article] Effects of acute and sub-chronic administrations of guanfacine on catecholaminergic transmissions in the orbitofrontal cortex (2019)
  • Author(s): Okada Motohiro、Fukuyama Kouji、Kawano Yasuhiro、Shiroyama Takashi、Suzuki Dai、Ueda Yuto
  • Journal Title: Neuropharmacology Volume: 印刷中 Pages: 107547-107547
  • DOI: 10.1016/j.neuropharm.2019.02.029
  • Peer Reviewed / Open Access
• [Journal Article] Cystine/Glutamate Antiporter and Aripiprazole Compensate NMDA Antagonist-Induced Dysfunction of Thalamocortical L-Glutamatergic Transmission (2018)
  • Author(s): Fukuyama Kouji、Hasegawa Toshiki、Okada Motohiro
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 11 Pages: 3645-3645
  • DOI: 10.3390/ijms19113645
  • Peer Reviewed / Open Access
• [Journal Article] Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites (2018)
  • Author(s): Fukuyama Kouji、Okada Motohiro
  • Journal Title: British Journal of Pharmacology Volume: 175 Issue: 22 Pages: 4253-4265
  • DOI: 10.1111/bph.14491
  • Peer Reviewed / Open Access
• [Journal Article] Incidence and Risk Factors of Postoperative Delirium following Pancreatic Surgery: Does the Administration of TJ-54 Reduce the Incidence of Delirium? (2017)
  • Author(s): Mizuno S, Takeuchi S, Kishiwada M, Mizutani N, Matsuda M, Sekoguchi N, Iizawa Y, Azumi Y, Kuriyama N, Usui M, Sakurai H, Maruyama K, Okuda M, Okada M, Isaji S.
  • Journal Title: Dig Surg Volume: - Issue: 1 Pages: 1-10
  • DOI: 10.1159/000456627
  • Peer Reviewed
• [Journal Article] Pre-operative Assessment of Psychological Characteristics and Mood States in Living Donor Kidney and Liver Transplantation. (2016)
  • Author(s): Nishikawa K, Hasegawa T, Usami A, Urawa A, Watanabe S, Mizuno S, Isaji S, Sugimura Y, Okada M.
  • Journal Title: Transplant Proc. Volume: 48 Issue: 4 Pages: 1018-1021
  • DOI: 10.1016/j.transproceed.2015.12.122
  • Peer Reviewed
• [Journal Article] Auditory change-related cerebral responses and personality traits. (2016)
  • Author(s): Tanahashi M, Motomura E, Inui K, Ohoyama K, Tanii H, Konishi Y, Shiroyama T, Nishihara M, Kakigi R, Okada M.
  • Journal Title: Neurosci Res Volume: 103 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Dysfunction of ventrolateral prefrontal cortex underlying social anxiety disorder: a multi-channel NIRS study (2015)
  • Author(s): Yokoyama C, Kaiya H, Kumano H, Kinou M, Umekage T, Yasuda S, Takei K, Nishikawa, M, Sasaki T, Nishimura Y, Hara N, Inoue K, Kaneko Y, Suzuki S, Tanii H, Okada M, Okazaki Y
  • Journal Title: NeuroImage: Clinical Volume: 8 Pages: 455-461
  • DOI: 10.1016/j.nicl.2015.05.011
  • Peer Reviewed / Open Access
• [Journal Article] Spontaneous epileptic seizures in transgenic rats harboring a human ADNFLE missense mutation in the β2-subunit of the nicotinic acetylcholine receptor. (2015)
  • Author(s): Yuko Shiba, Fumiaki Mori, Junko Yamada, Keisuke Migita, Yoshikazu Nikaido, Koichi Wakabayashi, Sunao Kaneko, Motohiro Okada, Shinichi Hirose, Shinya Ueno
  • Journal Title: Neuroscience research Volume: 100 Pages: 46-54
  • DOI: 10.1016/j.neures.2015.06.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 抗けいれん薬と抗てんかん薬としての作用機序 (2017)
  • Author(s): 岡田元宏
  • Organizer: 第５１回 日本てんかん学会
  • Invited
• [Presentation] CysLT1/CysLT2 受容体デュアル拮抗剤の抗けいれん作用につい (2017)
  • Author(s): 植田 勇人、岡田 元宏
  • Organizer: 第５１回 日本てんかん学会
• [Presentation] グリアとてんかん：アストロサイト Kir4.1 チャネルの病態解析を中心に (2017)
  • Author(s): 大野 行弘、福田 敦夫、岡田 元宏、小泉 修一
  • Organizer: 第５１回 日本てんかん学会
  • Invited