Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
Behav Brain Res. 2011 Nov 20;225(1):135-41. doi: 10.1016/j.bbr.2011.07.006. Epub 2011 Jul 8.
The association between pro-inflammatory cytokines and depression has been reported by many studies. However, the mechanisms by which inflammation affects mood are only partially understood. In this study, we detected depression-like behavior in a rat animal model which was induced inflammation in the spleen and brain by chronic mild stress (CMS). Wistar rats receiving CMS treatment for four weeks showed a variety of depression-like behavioral changes, including a significant reduction in sucrose preference and locomotion. Real-time RT-PCR was used to analyze the transcriptional regulation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-18) and anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) in hippocampus, cortex, hypothalamus and spleen. The result showed high expression of pro-inflammatory cytokines IL-1β, TNF-α and IL-6, and low expression of anti-inflammatory cytokines TGF-β and IL-10, thus higher ratio of TNF-α/IL-10 and IL-6/IL-10 in the brain of animal exposed to CMS. Simultaneously, brain derived neurotrophic factor mRNA decreased significantly in the hippocampus and hypothalamus of stressed rats. Immunofluorescence found that the BrdU Positive cells after CMS treatment significantly decreased in the hippocampus. These data suggested a crucial role of dysregulation between pro- and anti-inflammatory in CMS-induced depression, possibly because the imbalance of cytokines affects regeneration of neurons.
许多研究报告指出促炎细胞因子与抑郁症之间存在关联。然而，炎症影响情绪的机制仅部分得到理解。在这项研究中，我们在慢性轻度应激（CMS）诱导脾脏和大脑炎症的大鼠动物模型中检测到了类似抑郁的行为。接受 CMS 治疗四周的 Wistar 大鼠表现出多种类似抑郁的行为变化，包括蔗糖偏好和运动能力显著降低。实时 RT-PCR 用于分析海马体、皮质、下丘脑和脾脏中促炎细胞因子（IL-1β、TNF-α、IL-6 和 IL-18）和抗炎细胞因子（IL-10、IL-4 和 TGF-β）的转录调控。结果显示，促炎细胞因子 IL-1β、TNF-α 和 IL-6 的表达升高，抗炎细胞因子 TGF-β 和 IL-10 的表达降低，因此 CMS 暴露动物大脑中的 TNF-α/IL-10 和 IL-6/IL-10 比值更高。同时，应激大鼠海马体和下丘脑中的脑源性神经营养因子 mRNA 显著减少。免疫荧光发现，CMS 处理后 BrdU 阳性细胞在海马体中明显减少。这些数据表明促炎和抗炎之间失调在 CMS 诱导的抑郁症中起着关键作用，可能是因为细胞因子的失衡影响了神经元的再生。
