Xu Yongjun, Sheng Hui, Tang Zhiping, Lu Jianqiang, Ni Xin
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
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.
Behav Brain Res. 2015 Jul 15;288:71-8. doi: 10.1016/j.bbr.2015.04.017. Epub 2015 Apr 20.
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.
雌激素缺乏与抑郁症的发生有关。然而，雌激素调节抑郁样行为的潜在机制仍 largely 未知。炎症和吲哚胺-2,3-双加氧酶（IDO）已被证明在各种抑郁症模型中起关键作用。本研究的目的是调查雌激素缺乏诱导的抑郁样行为是否与大脑中的炎症和 IDO 激活有关。结果表明，卵巢切除导致雌性大鼠出现抑郁样行为，并导致海马中 5-羟色胺含量降低以及 IDO、干扰素-γ、白细胞介素-6、Toll 样受体（TLR）-4 和磷酸化核因子-κB（p65 亚基）水平升高，但前额叶皮质（PFC）中未出现这种情况。17β-雌二醇（E2）治疗改善了去卵巢大鼠的抑郁样行为，并恢复了海马中上述神经化学变化。偏相关分析表明，海马中磷酸化 p65、干扰素-γ 和白细胞介素-6 的水平与血清 E2 水平相关。我们的研究表明，雌激素抑制炎症并激活 IDO，并维持海马中 5-羟色胺水平，从而改善抑郁样行为。
