TRPV1 Regulates Reactive Microglia in AD through H4 Histone Lactation
Objective:The immune monitoring and phagocytosis function of microglia in Alzheimer's disease(AD)is progressively weakened and inflammatory activation occurs.Previous studies have reported that activation of transient receptor potential vanilloid type 1(TRPV1)channels alleviates microglial inflammatory activation and phagocytosis dysfunction in the brain of 3xTg mice,and the mech-anism of action is still unclear.Methods:First,the expression level and cellular localization of H4K12la in the nuclei of 3xTg mice brain cells were measured by western blotting and immunofluorescence experiments.Second,it was verified whether activation of TRPV1 could regulate the expression level of H4K12la in the nuclei of 3xTg mice brain cells.Finally,the effects of TRPV1 activation on mi-croglia inflammatory activation morphology and biomarkers were analyzed using Imaris software and flow cytometry.Results:Western blotting showed increased expression levels of H4K12la in the nuclei of 3xTg mice brain cells,and immunofluorescence experiments demonstrated that H4K12la co-localized with microglia.Activation of TRPV1 reduced the expression levels of H4K12la in microglia and alleviated inflammatory activation of microglia in the brain of 3xTg mice.Conclusions:These findings suggest that TRPV1 can alle-viate AD microglia inflammatory activation by inhibiting histone H4K12la expression.
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