Effects of spleen nerve denervation on depression–like phenotype, systemic inflammation, and abnormal composition of gut microbiota in mice after administration of lipopolysaccharide: A role of brain–spleen axis

Abstract

BackgroundAccumulating evidence suggests the role of brain–spleen axis as well as brain–gut–microbiota axis in inflammation-related depression. The spleen mediates anti-inflammatory effects of the vagus nerve which plays a role in depression. However, the role of spleen nerve in inflammation-related depression remains unclear. MethodsThe effects of the splenic nerve denervation (SND) in the depression-like phenotype, systemic inflammation, and abnormal composition of gut microbiota in adult mice after administration of lipopolysaccharide (LPS) were examined. ResultsLPS (0.5 mg/kg) caused depression-like phenotype, systemic inflammation, splenomegaly, increased expression of Iba1 (ionized calcium-binding adapter molecule 1) and decreased expression of postsynaptic density protein-95 (PSD-95) in the hippocampus in the sham-operated mice. In contrast, LPS did not produce depression-like phenotype, and abnormal expressions of Iba1 and PSD-95 in the hippocampus in the SND-operated mice. Furthermore, SND significantly blocked LPS-induced increased plasma levels of pro-inflammatory cytokine interleukin-6 although SND did not affect LPS-induced splenomegaly and increased plasma levels of tumor necrosis factor-α in mice. There were significant changes in several microbiota among the four groups. Interestingly, there were correlations between the relative abundance of several microbiota and Iba1 (or PSD-95) expression in the hippocampus. In addition, expression of Iba1 in the hippocampus was correlated with the relative abundance of several microbiota. LimitationsDetailed mechanisms are unclear. ConclusionsThese results suggest that the splenic nerve plays a role in inflammation-related depression, microglial activation in the hippocampus, and that gut microbiota may regulate microglial function in the brain via gut–microbiota–brain axis.