Pro- and anti-inflammatory cytokines expression in rat's brain and spleen exposed to chronic mild stress: involvement in depression.

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.