Glibenclamide modulates microglial function and attenuates Aβ deposition in 5XFAD mice

Severe neuroinflammation is known as a main pathology of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In these diseases, excessive microglial activation is one of the main causes of inflammation in the central nervous system. Therefore, inhibition of activated microglia may be suggested as a treatment for neuroinflammatory diseases. Glibenclamide, known as a therapeutics for type 2 diabetes in clinical trials has been shown to be effective in the inhibiting inflammatory conditions of various diseases. However, studies on the effects of glibenclamide for improving AD pathologies are little known. In this study, we tested glibenclamide on microglial cell line BV2 and 5XFAD mice. We found that glibenclamide significantly inhibited nitric oxide (NO) at 10 μM and 40 μM in BV2 cells induced by lipopolysaccharide (LPS) stimulation. In addition, we confirmed that 40 μM of glibenclamide reduced pro-inflammatory cytokines and proteins in the LPS-stimulated microglial cells. The anti-inflammatory effect of glibenclamide was further tested in APP/PS1 transgenic mouse. Although further analysis would be needed to confirm whether glibenclamide affects behavioral performance, our data suggests that glibenclamide may be a therapeutic option for AD treatment.