Title;
Potential involvement of mitochondrial dysfunction in major depressive disorder

 

Speaker:

Yuki Kanbe

Assisitant Professor, Graduate school of Medical and Dental Sciences, Kagoshima University

 

Abstract;
Mitochondria are the organelle in the cells, and are found in almost all of eukaryotic cells. We call mitochondria as “power plant” because mitochondria produce most of the cellular energy, ATP. Cells harboring large and complex structures such as neuron are very sensitive to mitochondiral defect. Indeed, nervous system frequently malfunctions in mitochondrial disease which is caused by inherited mitochondrial defect. Therefore, mitochondria may play critical role in the pathophysiology of the central nervous system.
Recent 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.

 

References;
1. Y. Kambe and A. Miyata, Potential Involvement of Mitochondrial Dysfunction in Major Depressive Disorder: Recent Evidence. Arch Depress Anxiety, 2015. 1(1): p. 019-028.
2. Y. Kambe and A. Miyata, Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice. Neurosci Lett, 2015. 588: p. 166-71.
3. Y. Kambe and A. Miyata, Role of Mitochondrial Activation in PACAP Dependent Neurite Outgrowth. J Mol Neurosci, 2012. 48(3): p. 550-557.