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

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830054
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kagoshima University
• Principal Investigator: KAMBE Yuki 鹿児島大学, 医歯(薬)学総合研究科, 助教 (60549913)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ミトコンドリア / 新規創薬ターゲット / うつ病 / 変性タンパク質ストレス

Outline of Final Research Achievements

Many evidences strongly 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 spastic paraplegia 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 in the tail suspension and forced swim tests, decreased oxygen consumption rate, and increased levels of molecules associated with UPRmt, such as Hspa9, Hspd1, Ubl5, Abcb10, and ClpP. All of the UPRmt-related molecules were significantly correlated with depressive-like behavior in the forced swim test. 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

神経薬理学, 分子薬理学