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Overactive microglia and severe neuroinflammation play crucial roles in the development of major depressive disorder. Preconditioning with lipopolysaccharide (LPS) provides protection against severe neuroinflammation. However, administering high doses of LPS to mice triggers depressive symptoms. Therefore, the optimal dose of LPS preconditioning needs to be determined by further experiments. LPS preconditioning is an effective agent in anti-inflammation and neuroprotection, but the mechanism by which LPS preconditioning acts in depression remain unclear. This study finds that the anti-inflammation mechanism of low-dose LPS preconditioning is mainly dependent on G-protein-coupled receptor 84 (GPR84). We use low-dose LPS for preconditioning and re-challenged mice or BV2 microglia with high-dose LPS. In addition, RNA-seq is used to explore underlying changes with LPS preconditioning. Low-dose LPS preconditioning reduces the expression of pro-inflammatory mediators and inhibits microglial activation, as well as suppresses the depressive-like behavior when the mice are re-challenged with high-dose LPS. Further investigation reveals that the tolerance-like response in microglia is dependent on the GPR84. Here, we show that low-dose LPS preconditioning can exert anti-inflammation effects and alleviates inflammation-induced depressive-like behavior in mice. As a potential therapeutic target for depression, LPS preconditioning needs to be given further attention regarding its effectiveness and safety. [ABSTRACT FROM AUTHOR]

Hou G, Tang M, Yan L, Wang M. Changes of ultrastructure and downregulation of heat shock protein 70 and fibroblast growth factor 2 in gastric mucosa of rats with depressive-like behaviour. Objective: To understand the underlying mechanism of gastric symptoms in patients with depressive disorder. Methods: This study tested in the rat depression model evoked with chronic mild stress whether the microstructure gastric mucosa is injured using scanning electronic microscopy and transmission electronic microscopy (TEM). In addition, the expression of heat shock protein 70 (HSP70) and fibroblast growth factor 2 (FGF2) proteins in the gastric mucosa were measured by Western blotting. Results: We found that the gastric epithelial cells were ruptured and the gastric pits were widened in rats with depression. The amount of mucous granules was also reduced in the surface mucous cells. Moreover, parietal cells became active, and the secretory canaliculi were magnified. Expression of HSP70 and FGF2 was reduced in the gastric mucosa. Conclusions: These findings suggested that gastric symptoms in rats with depressive-like behaviour were caused by the injury of the gastric mucosa, AQ1 and HSP70 and FGF2 may be key molecules in the pathogenesis. [ABSTRACT FROM AUTHOR]

Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB’s therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20 mg/kg, intraperitoneally, once daily) for 3 weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40 µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro , and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Central LPS treatment did not aggravate stress-induced depressive-like behavior. [•] Central IL-10 treatment reversed stress-induced depressive-like behavior. [•] Chronic central LPS treatment induced significant depressive-like behavior. [•] Chronic central IL-10 treatment itself had no effect on behavior. [ABSTRACT FROM AUTHOR]