Neuroinflammatory transcriptional signatures in the entorhinal cortex based on lipopolysaccharide-induced depression model in mice

The inflammation and immune hypothesis of major depressive disorder (MDD) explains the mechanism of neuroinflammatory response to promote depression-like behaviors and provides targets for immunotherapy. Previous studies revealed that the neuronal function of the entorhinal cortex (EC) was relative to the depression symptoms in MDD. However, it remains largely unknown what role of neuroinflammation plays in the EC. Hence, we used immunofluorescence to determine c-Fos expression in the EC of lipopolysaccharide (LPS)-treated mice. Mice model was constructed of 10-day LPS treatment, and depression-related behaviors were assessed. We used gene expression microarray to determine differentially expressed genes (DEGs) in the EC of LPS group comparing to control group, and molecular verification was performed by quantitative real-time PCR and Western blot. We found that c-Fos expression was significant reduced in the two layers (Lateral 3.25 mm and 3.00 mm) of the EC in LPS-treated mice compared to saline-treated mice. Mice in LPS group exhibited depression- and anxiety-like behaviors in chronic model. Gene expression analyses identified 339 DEGs in the EC between LPS and control group. The molecular verification showed activation of IL-1R1/NF-κB/CCL5 signaling and upregulation of markers of astrocyte (GFAP) and microglia (AIF1 and CD86) in the EC. Our results suggested that LPS-induced neuroinflammation inhibited neuronal activity in the EC of mice, and that activation of IL-1R1/NF-κB/CCL5 signaling could be involved in the neuroinflammation in the EC of LPS-treated depression model.