Investigation of microglial activation through noradrenaline in the process of neurodegenerative disease

• Project/Area Number: 24500465
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Nippon Medical School
• Principal Investigator: SUGAMA Shuei 日本医科大学, 医学部, 講師 (70302461)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Makoto (50189502) ; TAKENOUCHI Takato (20292518)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ミクログリア / ストレス / ノルアドレナリン / 青斑核 / アドレナリン受容体 / 脳内免疫 / 慢性ストレス / 黒質 / ドーパミン / ニトロタイロシン / 酸化ストレス / 神経免疫 / 神経科学 / 海馬 / 視床下部 / 副腎ステロイド / 脳内炎症

Outline of Final Research Achievements

We have demonstrated the first evidence that acute stress could induce morphological microglial activation in the brain. The goal of this study was to investigate the mechanism how the microglial activation is triggeredd by exposures to acute stress. We found that Dopamine beta Hydroxylase (DBH), an enzyme required for the synthesis of noradrenaline in the brain, is significantly elevated in the hippocampus, thalamus, and hypothalamus in response to acute stress. In addition, we found that DBH immunoreactive fibers surround microglial cells. Those microglial cells were found to be positive to beta 1 and beta 2 Adrenergic Receptor (AR). We suggest that microglia may be modulated through noradrenaline during the time of acute stress.

Research Products

• [Journal Article] Disease-Modifying Effect of Adiponectin in Model of a-Synucleinopathies (2014)
  • Author(s): Sekiyama K, Waragai M, Akatsu H, Sugama S, Takenouchi T, Takamatsu Y, Fujita M, Sekigawa A, Rockenstein E, Inoue S, La Spada AR, Masliah E, Hashimoto M
  • Journal Title: Ann Clin Transl Neurol Volume: 1 Pages: 479-489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Corticosteroids limit microglial activation occurring during acute stress (2012)
  • Author(s): Sugama S, Takenouchi T, Fujita M, Kitani H, Conti B, Hashimoto M
  • Journal Title: Neuroscience Volume: 232 Pages: 13-20
  • DOI: 10.1016/j.neuroscience.2012.12.012
  • Peer Reviewed
• [Journal Article] IL-13Ra1 expression in dopaminergic neurons contributes to thier oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide (2012)
  • Author(s): Morrison BE, Marcondes MC, Nomura DK, Sanchez-Alavez M, Sanchez-Gonzalez A, Saar I, Kim KS, Bartfai T, Maher P, Sugama S, Conti B
  • Journal Title: J Immunol Volume: 15 Issue: 12 Pages: 5498-5502
  • DOI: 10.4049/jimmunol.1102150
  • Peer Reviewed
• [Journal Article] Cytochalasin D enhances the accumulation of a protease-resistant form of prion protein in ScN2a Cells: Involvement of PI3 kinase/Akt signaling pathway. (2012)
  • Author(s): Takenouchi T. et al.
  • Journal Title: Cell Biol. Int. Volume: 36 Issue: 12 Pages: 1223-1231
  • DOI: 10.1042/cbi20120329
  • Peer Reviewed
• [Journal Article] Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H b-synuclein (2012)
  • Author(s): S ekiyama K, Fujita M, Sekigawa A, Takamatsu Y, Waragai M, Takenouchi T, Sugama S, Hashimoto M
  • Journal Title: Neurosci Lett Volume: 515(1) Issue: 1 Pages: 97-101
  • DOI: 10.1016/j.neulet.2012.03.037
  • Peer Reviewed
• [Presentation] Stress-induced microglial activation may be triggered by noradrenergic neurons (2015)
  • Author(s): 洲鎌 秀永、柿沼 由彦
  • Organizer: 日本生理学会（第９２回）
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 急性拘束ストレスモデルを用いた活性化ミクログリアとcFos発現ニューロンのトポグラフィー分析 (2014)
  • Author(s): 洲鎌秀永
  • Organizer: 第９１回日本生理学会
  • Place of Presentation: 鹿児島市
• [Presentation] Corticosteroids limit microglial activation occurring during acute stress (2013)
  • Author(s): 洲鎌 秀永
  • Organizer: 日本生理学会（第90回）
  • Place of Presentation: 東京