D-β-hydroxybutyrate inhibits microglial activation in a cell activation model in vitro

Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis (MS) and Parkinson's disease (PD), and is a key target for developing therapeutic strategies for these diseases. Ketogenic diet (KD), which is able to inhibit microglial activation in substantia nigra pars compacta of mice, has been shown effective in a mouse model of PD, possibly through increasing D-β-hydroxybutyrate (D-β-HB), a major component of ketone bodies. To verify this, we developed an in vitro model of microglia activation with a microglia line, BV-2, and investigated how D-β-HB have an effect on the LPS-stimulated BV-2 cells. We found D-β-HB is able to recover the cell viability, and inhibit the production of inflammatory mediators and cytokines such as ROS, nitrite, IL-Iβ, TNF-α, and IL-6, which otherwise were increased in LPS-stimulated BV-2 cells. We conclude that the LPS induced BV-2 cells activation is a valid in vitro model of microglia activation. D-β-HB is able to suppress the activation of BV-2 cells, which might account for one of the possible reasons of KD therapy on the PD model.