Alteration of autophagy signaling in the brain by psychiatric treatments

• Project/Area Number: 15K09816
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tohoku Medical and Pharmaceutical University (2017); National Defense Medical College (2015-2016)
• Principal Investigator: NIBUYA Masashi 東北医科薬科大学, 医学部, 講師 (00228256)
• Co-Investigator(Kenkyū-buntansha): 清水 邦夫 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、共同利用研究施設、病院並びに防衛, 防衛医学研究センター 行動科学研究部門, 教授 (00531641) ; 戸田 裕之 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、共同利用研究施設、病院並びに防衛, 精神科学, 講師 (00610677) ; 鈴木 豪 国立研究開発法人宇宙航空研究開発機構, 有人宇宙技術部門, 主任医長 (50649035)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: autophagy / endocytosis / BDNF / TrkB / ECT / stress / hippocampus / lipid raft / 電気けいれん療法 / depression / stress resilience / neural plasticity / membrane trafficking / hippocampal region / antidepressant

Outline of Final Research Achievements

Analyses revealed significantly upregulated expression of endocytosis-related proteins following 10-day electroconvulsive seizure (ECS) treatment in rat hippocampal homogenates and hippocampal lipid raft fractions. We consider that the membrane trafficking machinery that transports functional proteins in the neuronal cells and from or into the synaptic membranes is one of the new candidates supporting the cellular and behavioral neuroplastic profiles of ECT administrations.
The exact activation of BDNF/TrkB signaling following multiple ECS treatments has not been well elucidated. We demonstrated increased phosphorylation as well as decreased expression of the full-length TrkB receptor in both dorsal and ventral hippocampal regions of rats after a 10-day ECS treatment. Our results indicate that the hippocampal BDNF/TrkB signaling pathway is activated by ECS treatments despite the ligand-induced down-regulation of the full-length TrkB receptor.

Research Products

• [Journal Article] Activated brain-derived neurotrophic factor/TrkB signaling in rat dorsal and ventral hippocampi following 10-day electroconvulsive seizure treatment (2017)
  • Author(s): Enomoto Shingo、Shimizu Kunio、Nibuya Masashi、Suzuki Eiji、Nagata Kiyoshi、Kondo Takashi
  • Journal Title: Neuroscience Letters Volume: 660 Pages: 45-50
  • DOI: 10.1016/j.neulet.2017.09.011
  • Peer Reviewed
• [Journal Article] Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue. (2016)
  • Author(s): Aoki, R., Kobayashi, N., Suzuki, G., Kuratsune, H., Shimada, K., Oka, N., Takahashi, M., Yamadera, W., Iwashita, M., Tokuno, S., Nibuya, M., Tanichi, M., Mukai, Y., Mitani, K., Kondo, K., Ito, H., Nakayama, K.
  • Journal Title: Biochem. Biophy. Res. Commun. Volume: 478 Issue: 1 Pages: 424-430
  • DOI: 10.1016/j.bbrc.2016.07.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased Expression of Endocytosis-Related Proteins in Rat Hippocampus Following 10-Day Electroconvulsive Seizure Treatment. (2016)
  • Author(s): Enomoto S, Shimizu K, Nibuya M, Toda H, Yoshino A, Suzuki E, Kondo T, Fukuda H
  • Journal Title: Neurosci Lett Volume: in press Pages: 85-91
  • DOI: 10.1016/j.neulet.2016.05.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neuroprotective effects of adenosine deaminase in the striatum (2016)
  • Author(s): ２.Tamura R, Ohta H, Satoh Y, Nonoyama S, Nishida Y, Nibuya M
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 36 Issue: 4 Pages: 709-720
  • DOI: 10.1177/0271678x15625077
  • Peer Reviewed
• [Journal Article] Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder. (2015)
  • Author(s): Toda H, Inoue T, Tsunoda T, Nakai Y, Tanichi M, Tanaka T, Hashimoto N, Takaesu Y, Nakagawa S, Kitaichi Y, Boku S, Tanabe H, Nibuya M, Yoshino A, Kusumi I.
  • Journal Title: Psychiatry Res Volume: 236 Pages: 142-7
  • DOI: 10.1016/j.psychres.2015.12.016
  • Peer Reviewed
• [Journal Article] Low-level laser therapy for prevention of noise-induced hearing loss in rats. (2015)
  • Author(s): Tamura A, Matsunobu T, Mizutari K, Niwa K, Kurioka T, Kawauchi S, Satoh S, Hiroi S, Satoh Y, Nibuya M, Tamura R, Shiotani A
  • Journal Title: Neurosci Lett Volume: 595 Pages: 81-6
  • DOI: 10.1016/j.neulet.2015.03.031
  • Peer Reviewed
• [Journal Article] The structural equation analysis of childhood abuse, adult stressful life events, and temperaments in major depressive disorders and their influence on refractoriness. Neuropsychiatr Dis Treat. (2015)
  • Author(s): Toda H, Inoue T, Tsunoda T, Nakai Y, Tanichi M, Tanaka T, Hashimoto N, Nakato Y, Nakagawa S, Kitaichi Y, Mitsui N, Boku S, Tanabe H, Nibuya M, Yoshino A, Kusumi I.
  • Journal Title: Neuropsychiatr Dis Treat Volume: 11 Pages: 2079-90
  • DOI: 10.2147/ndt.s82236
  • Peer Reviewed / Open Access