Minocycline Ameliorates Staphylococcus aureus-Induced Neuroinflammation and Anxiety-like Behaviors by Regulating the TLR2 and STAT3 Pathways in Microglia

Background: Anxiety disorders are the most common mental illnesses. S. aureus is a Gram-positive opportunistic pathogen most commonly associated with anxiety-like behaviors. Minocycline ameliorates Gram-negative bacterial LPS-induced anxiety-like behaviors by suppressing microglia activation. However, the effects of minocycline on anxiety-like behaviors caused by S. aureus infections have received little attention. In this study, we aimed to investigate the molecular mechanism and effect of minocycline on anxiety-like behaviors caused by S. aureus infection. Methods: BV2 and N9 microglial cells were treated in vitro. The effects of minocycline on lipoteichoic acid (LTA)-stimulated inflammatory responses, STAT3 activation, and GLS1 expression were assessed using Western blotting, and cytokine secretion was determined using an ELISA. A mouse model was used to evaluate the capacity of minocycline to ameliorate anxiety-like behaviors caused by S. aureus infection. Results: We found that >= 100 mu mol/L of minocycline remarkably attenuated LTA-induced TLR2 signaling pathway activation and proinflammatory cytokine expression in microglial cells. Minocycline prevented LTA-stimulated STAT3 activation and GLS1 expression in vitro. LTA-induced TLR2, TNF-alpha, IL-6, and GLS1 expression was markedly reduced by the inhibition of STAT3 phosphorylation. Mice were pretreated with 50 mg/kg of minocycline, significantly attenuating microglial activation and neuroinflammation. Minocycline also effectively alleviated the anxiety-like behaviors induced by S. aureus infection. Conclusions: Our findings indicate that minocycline alleviates S. aureus infection-induced anxiety-like behaviors by suppressing microglia activation.