title: Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency.
abstract: Estrogen deficiency is involved in the development of depression. However, the mechanism underlying estrogen modulates depression-like behavior remains largely unknown. Inflammation and indoleamine-2,3-dioxygenase (IDO) have been shown to play pivotal roles in various depression models. The objective of the present study was to investigate whether estrogen deficiency-induced depression-like behavior is associated with inflammation and IDO activation in brain. The results showed that ovariectomy resulted in depression-like behavior in female rats and caused a decrease in 5-HT content and an increase in levels of IDO, IFN-γ, IL-6, toll like receptor (TLR)-4 and phosphorylated NF-κB (p65 subunit) in hippocampus but not in prefrontal cortex (PFC). 17β-Estradiol (E2) treatment ameliorated depression-like behavior and restored above neurochemical alternations in hippocampus in ovariectomized rats. Partial correlation analysis showed that the levels of phosphorylated p65, IFN-γ and IL-6 in hippocampus correlated to serum E2 level. Our study suggests that estrogen inhibits inflammation and activates of IDO and maintains 5-HT level in hippocampus, thereby ameliorating depression-like behavior.
authors.affiliation: Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.affiliation: School of Kinesiology, The key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, 399 Changhai Road, Yangpu District, Shanghai 200438, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Tang
authors.affiliation: School of Kinesiology, The key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, 399 Changhai Road, Yangpu District, Shanghai 200438, China. Electronic address: lujianqiang@sus.edu.cn.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: nixin@smmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D010052:Ovariectomy; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004967:Estrogens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015850:Interleukin-6; D016328:NF-kappa B; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C063447:p65 oncofetal mRNA transport protein, rat; D012701:Serotonin; D007371:Interferon-gamma
keywords: Depression; Estrogen; Indoleamine-2,3-dioxygenase (IDO); Inflammation