Central mechanisms for continuous responses of sympathetic nervous system to stress exposure

• Project/Area Number: 20K07982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Aichi Medical University
• Principal Investigator: YAMAGUCHI Naoko 愛知医科大学, 医学部, 准教授 (50380324)
• Co-Investigator(Kenkyū-buntansha): 岡田 尚志郎 愛知医科大学, 医学部, 教授 (40203989) ; 呉 ユー秋 愛知医科大学, 医学部, 助教 (40717154)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ストレス / 交感神経系 / カテコールアミン / 視床下部室傍核 / コルチコトロピン放出因子 / CRF / 室傍核

Outline of Research at the Start

過剰なストレス応答は、うつ病などストレス関連疾患の発症の契機となりうる。私たちはこれまで、交感神経系活性化の脳内調節機構を解析してきた。その過程で、コルチコトロピン放出因子（CRF）を起点とする脳内経路がストレス応答の異常な持続に関与する可能性が示唆されたが、その詳細は未だ不明である。本研究ではストレスモデルラットを用いて、CRF関連経路とその調節因子がストレス応答の持続に及ぼす影響を明らかにする。

Outline of Final Research Achievements

Stress exposure causes various stress responses including sympathetic activation. Continuous stress responses are one of risk factors associated with stress-related diseases such as depression. We have already reported that corticotropin-releasing factor (CRF) in the brain is important for continuous sympathetic activation, and that brain prostanoids are related to CRF-induced sympathetic activation.
In this study, we examined the mechanisms in the brain, especially in the paraventricular hypothalamic nucleus (PVN), of sympathetic activation during acute and repeated exposure to stress. Our results demonstrated that sympathetic responses during chronic stress exposure were different from those in acute stress, and that brain prostanoids were associated with such differences.

Academic Significance and Societal Importance of the Research Achievements

ストレス反応は本来、生体の防御機構である。しかし、過剰なストレス反応はストレス不適応をもたらし、さらにはうつ病などのストレス関連疾患の発症の契機ともなりうる。このような過剰かつ持続するストレス反応をもたらす脳内の調節機構については、交感神経反応制御の観点では未だ不明な点も多い。
本研究の成果から、ストレス強度による交感神経反応の違いや脳内調節に関与する因子についての知見が得られた。ストレス応答の調節メカニズムに関する基礎的知見蓄積の一助となり、将来的にストレス関連疾患の予防・治療法の開発に繋がると考えられる。

Research Products

• [Journal Article] Glucose infusion suppresses acute restraint stress-induced peripheral and central sympathetic responses in rats. (2022)
  • Author(s): Yamaguchi N, Kakinuma Y, Yakura T, Naito M, Okada S.
  • Journal Title: Auton. Neurosci. Volume: 239 Pages: 102957-102957
  • DOI: 10.1016/j.autneu.2022.102957
  • Peer Reviewed / Open Access
• [Journal Article] Thromboxane A2 in the paraventricular hypothalamic nucleus mediates glucoprivation-induced adrenomedullary outflow. (2020)
  • Author(s): Tachi M, Yamaguchi N, Okada S.
  • Journal Title: Eur. J. Pharmacol. Volume: 875 Pages: 173034-173034
  • DOI: 10.1016/j.ejphar.2020.173034
  • Peer Reviewed
• [Presentation] Astrocytes in the PVN are involved in corticotropin-releasing factor-induced sympathetic activation in rats. (2022)
  • Author(s): Yamaguchi N, Okada S.
  • Organizer: 第96回日本薬理学会年会
• [Presentation] ATP-sensitive K+ channel activation in the brain is involved in elevation of plasma levels of adrenaline. (2022)
  • Author(s): Okada S, Yamaguchi N.
  • Organizer: 第96回日本薬理学会年会
• [Presentation] Yokukansan, a traditional Japanese medicine, suppresses stress-induced sympathetic activation and central responses to stress in rats. (2022)
  • Author(s): Yamaguchi N, Fujikawa M, Okada S.
  • Organizer: 第95回日本薬理学会年会