Dextromethorphan Suppresses Lipopolysaccharide-Induced Epigenetic Histone Regulation in the Tumor Necrosis Factor-α Expression in Primary Rat Microglia

الملخص EN

The activation of microglial cells plays an important role in the cascade of events leading to inflammation-mediated neurodegenerative disorders.

Precision therapeutics require that adjunctively feasible drugs be found to prevent microglial cell activation and prevent inflammation-mediated neuronal injury.

Dextromethorphan (DM) has been reported to possess neuroprotective effects in lipopolysaccharide- (LPS-) stimulated animals; however, it remains unclear whether epigenetic regulatory mechanisms in microglial cells are involved in such DM-mediated neuroprotective effects.

In this study, DM simultaneously suppressed LPS-induced activation of tumor necrosis factor- (TNF-) α expression and subsequent caspase-3 signaling in primary microglial cells associated with notable morphological changes.

Furthermore, therapeutic action sites of DM involved differential enhanced trimethylation of H3K4 modifications in the promoter region of tnf-α gene locus in primary microglial cells.

In summary, DM may exert neuroprotective and anti-inflammatory effects through differential epigenetic histone modifications of TNF-α expression in microglial cells and might therefore raise the possibility of providing an adjunctively beneficial role for a tentative therapeutic strategy in neurodegenerative diseases resulting from inflammation.