Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice

Statins play a beneficial role in the treatment of coronary artery disease and are widely prescribed to prevent hypercholesterolemia. Previous studies have demonstrated that statins also have anti-inflammatory and immunomodulatory properties, and these are being explored for potential benefits in depression. However, the role of statins in the treatment of depression has not been well examined.

We investigated the effects of simvastatin on depressive behaviors and neuroinflammation in lipopolysaccharide (LPS) and chronic mild stress (CMS) induced depression model in mice. Sucrose preference test (SPT), forced swimming test (FST), novelty-suppressed feeding test (NSFT) were used to detect the depressive behaviors. The microglial activation was detected by immunohistochemistry analysis and the pro-inflammatory cytokines expressions including IL-1β, TNF-α and IL-6 were examined by Western blot analysis.

Our data indicated that oral administration of simvastatin at 20 mg/kg significantly prevented and ameliorated depressive behaviors reflected by better performance in the SPT, FST and NSFT. Moreover, simvastatin markedly prevented and ameliorated LPS and CMS-induced neuroinflammation, as shown by the suppressed activation of microglia in hippocampus and decreased hippocampal pro-inflammatory cytokines expressions including IL-1β, TNF-α, IL-6, which might be mediated via the inhibition of NF-κB pathway, as shown by the decreased nuclear NF-κB p65 expression.

The interpretation of the evidence of a positive treatment effect of simvastatin on the depressive manifestations, multifaceted etiology of depression, and confirmation of this finding from animal models to humans is needed.

These results suggest that simvastatin has the potential to be employed as a therapy for depression associated with neuroinflammation.