The role of the amygdala in depression

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08079
• 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: Health Sciences University of Hokkaido
• Principal Investigator: IZUMI Takeshi 北海道医療大学, 薬学部, 教授 (60312360)
• Co-Investigator(Kenkyū-buntansha): 鹿内 浩樹 北海道医療大学, 薬学部, 講師 (00632556)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: うつ病 / 動物モデル / ストレス / 扁桃体 / FKBP5 / Akt / mTOR

Outline of Final Research Achievements

We measured depression-associated molecules such as those involved with the hypothalamic-pituitary-adrenal system, PI3K/Akt/mTOR system and GSK3β/β-catenin/Wnt system in the brains and blood of repeated restraint stress (RS7) rats, an animal model of depression. We found increased blood glucocorticoids (GC), increased FKBP5 (negative feedback regulator of GC) and increased phosphorylation of Akt (Ser-483) in the amygdala, and decreased phosphorylation of mTOR active complex mTORC1 in the hippocampus (Ser-2448). No changes in molecules involved in the GSK3β/β-catenin/Wnt system were detected. In the future, we would like to clarify the pathophysiology of depression by investigating the upstream and downstream events resulting from these molecular changes.

Free Research Field

精神薬理学

Academic Significance and Societal Importance of the Research Achievements

抗うつ薬によるうつ病の回復率は60%程度であり、更に有効な治療法の開発のために、うつ病の病態解明が必要である。今回、我々はうつ病モデルラットの脳でうつ病関連分子の系統的な評価を行い、視床下部－下垂体－副腎系の調節分子であるFKBP5と、PI3K/Akt/mTOR系の分子であるAktおよびmTORC1が変化している所見を得た。今後、これらの分子変化をさらに追及し、うつ病の病態変化を解明したい。