Changes of inflammatory mediator’s expression in the rat medial prefrontal cortex (mPFC) after minocycline treatment in lipopolysaccharide induced neuroinflammation rat model

Abstract Introduction: Minocycline has been showed can ameliorates neuroinflammation that was encountered in many neurodegenerative diseases. This study aims to investigate the expression of inflammatory mediators in the rat medial prefrontal cortex (mPFC) after minocycline treatment in lipopolysaccharide (LPS) induced neuroinflammation rat model. Methods Adult male Sprague Dawley (SD) rats (N = 50) were divided into 5 groups: 1) control, 2) LPS (5 mg/kg), 3) LPS + minocycline (25 mg/kg), 4) LPS + minocycline (50 mg/kg) and 5) LPS + memantine (10 mg/kg). Intraperitoneal minocycline and memantine were given daily for 14 days, while LPS injection was given once on 5th day. Western blot and immunohistochemistry were used to assess density and expression of TLR-4, nuclear factor kappa-B (NF-kB), tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in the medial prefrontal cortex (mPFC) of rats. Results Findings displayed that minocycline significantly decreased expression and density of TLR-4, NF-kB, TNF-α and COX-2 proteins that were comparable to memantine in mPFC of SD rat injected with single intraperitoneal LPS. Interestingly, the anti-inflammatory effects of minocycline 50 mg/kg were significantly more than minocycline 25 mg/kg. Conclusion This study suggested that minocycline can modulated LPS-induced neuroinflammation in dose-dependent manner in the mPFC area. Thus, it is suggested that minocycline can be used as potential preventive-therapeutic drug for neuroinflammatory diseases such as depression and anxiety.