Minocycline mitigates tau pathology via modulating the TLR-4/NF-Ðºß signalling pathway in the hippocampus of neuroinflammation rat model.
Neurol Res
; 46(3): 261-271, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38122814
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-кß), tumour necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry.RESULTS:
Minocycline, like memantine, prevented LPS-induced increasein phosphorylated tau protein level suggested via reduced density and expression of TLR-4, NF-кß, TNF-αand 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 can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
/
Minociclina
Límite:
Animals
Idioma:
En
Revista:
Neurol Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Malasia