Minocycline mitigates tau pathology via modulating the TLR-4/NF-кβ signalling pathway in the hippocampus of Alzheimer disease’s rat model

Abstract Introduction: The neuroinflammatory response was seen to impact the formation of phosphorylated tau protein in Alzheimer’s disease (AD). This study aims to investigate the molecular mechanism of minocycline in reducing phosphorylated tau protein formation in the hippocampus of lipopolysaccharide (LPS)-induced rats. Methods Fifty adult male Sprague Dawley (SD) rats were randomly allocated to 1 of 5 groups: control, LPS (5 mg/kg), LPS + minocycline (25 mg/kg), LPS + minocycline (50 mg/kg) and LPS + memantine (10 mg/kg). Minocycline and memantine were administered intraperitoneally (i.p) for two weeks, and LPS was injected i.p. once on day 5. ELISA was used to determine the level of phosphorylated tau protein in SD rats' hippocampal tissue. The density and expression of Toll-like receptor-4 (TLR-4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кβ), tumour necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry. Results Minocycline, like memantine, prevented LPS-induced increase in phosphorylated tau protein level via reduced density and expression of TLR-4, NF-кβ, TNF-α and COX-2 proteins in rat hippocampal tissue. Interestingly, higher doses were shown to be more neuroprotective than lower doses. Conclusion This study suggests that minocycline suppresses the neuroinflammation signalling pathway and decreased phosphorylated tau protein formation induced by LPS in a dose-dependent manner. Minocycline has been recommended can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.