Sulforaphane triggers a functional elongation of microglial process via the Akt signal

Microglia are a kind of innate immune cells in the nervous system. The amoeboid morphology in microglia indicates a pro-inflammatory status, while their ramified morphologies are associated with anti-neuroinflammation. Recently, we and others have reported that drugs that trigger microglial process elongation may be beneficial for neuroinflammation inhibition. In this study, we found that sulforaphane (SFN), a compound extracted from broccoli sprouts, promotes primary cultured microglial process elongation in both normal and pro-inflammatory conditions in a reversible manner. This pro-elongation effect of SFN was also observed in the prefrontal cortex in vivo and accompanied with an attenuation of pro-inflammatory response as well as an enhancement of anti-inflammatory response in primary cultured microglia. Mechanistic studies revealed that the SFN treatment increased Akt phosphorylation levels in primary cultured microglia and Akt inhibition blocked the effect of SFN on microglial process elongation, suggesting that the regulation of microglial process by SFN is mediated by Akt activation. Functional studies showed that Akt inhibition reversed the effect of SFN on both pro- and anti-inflammatory responses in lipopolysaccharide (LPS)-stimulated microglia. In an inflammation model in vivo, SFN pretreatment not only prevented LPS-induced retractions of microglial process in the prefrontal cortex, but improved LPS-induced behavioral abnormalities in mice, including the increase in immobility time in the tail suspension test and forced swim test as well as the decrease in sucrose preference. These results indicate that the SFN inhibits microglial activation and neuroinflammation-triggered behavioral abnormalities likely through triggering Akt-mediated microglial process elongation.