Forkhead box O transcription factors as possible mediators in the development of major depression.
Forkhead box O (FoxO) transcription factors play important roles in cellular physiology and biology. Recent findings indicate that FoxOs are also involved in the development of major depressive disorder. Alterations in the upstream molecules of FoxOs, such as brain derived neurotrophic factor or protein kinase B, have been linked to depression. Antidepressants, such as imipramine and venlafaxine, modify the FoxOs phosphorylation. Furthermore, FoxOs could be regulated by serotonin and norepinephrine receptor signaling as well as the hypothalamic-pituitary-adrenal axis, all of which are involved in the pathogenesis of depression. FoxOs also regulate neuronal morphology, synaptogenesis and adult hippocampal neurogenesis, which are viewed as candidate mechanisms for the etiology of depression. In this review, we emphasize the possible roles of FoxOs during the development of depression and make some strategic recommendations for future research. We propose that FoxOs and its signaling pathways may constitute potential therapeutic targets in the treatment of depression.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Haitao
H
Wang
Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Rémi
R
Quirion
School of Pharmacy, The University of Queensland, QLD 4072, Australia.
Peter J
PJ
Little
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Yufang
Y
Cheng
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Zhong-Ping
ZP
Feng
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Hong-Shuo
HS
Sun
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: jpx@smu.edu.cn.
Jiangping
J
Xu
Faculty of Health Sciences, University of Macau, Taipa, Macau, China. Electronic address: wenhuazheng@umac.mo.
Wenhua
W
Zheng
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D051858:Forkhead Transcription Factors
Antidepressants; FoxO; Major depression; Neurogenesis; Neuronal atrophy; PI3K/Akt