Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Kagoshima University
• Principal Investigator: Kambe Yuki 鹿児島大学, 医歯学域医学系, 講師 (60549913)
• Co-Investigator(Kenkyū-buntansha): 宮田 篤郎 鹿児島大学, 医歯学域医学系, 教授 (60183969) ; 栗原 崇 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 神経生物学 / うつ病 / ミトコンドリア / UPRmt

Outline of Final Research Achievements

Many evidences suggest that a mitochondrial deficit is implicated in major depression. A mitochondrial deficit leads to mitochondrial stress responses, including the mitochondrial unfolded protein response (UPRmt), which is associated with certain brain disorders such as Alzheimer’s and Parkinson’s disease. However, there is no evidence regarding the relationship between depressive disorder and UPRmt. Mice treated with chronic restraint stress showed significant depressive-like behaviors, and increased levels of molecules associated with UPRmt. Thus, the present study is the first to reveal a relationship between the UPRmt and depressive disorder, suggesting that the UPRmt is a potential drug target for depressive disorders.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

うつ病患者の3割は既存の抗うつ薬に耐性を示す難治性うつ病である事から，異なる作用点を持つ薬剤の創出は急務である．ミトコンドリア変性タンパク質ストレスレスポンス (UPRmt) はミトコンドリア内におけるタンパク質の品質管理システムであり，うつ病にUPRmtが関与するか否かについてこれまで検討されていなかった．申請者は，UPRmtが有用なうつ病治療薬ターゲットとなりうる可能性を明らかにした．