抄録
Cannabidiol (CBD), the major non-psychotropic phytocannabinoid, induces apoptosis in immune cells, including primary and immortalized lymphocytes and monocytes. However, contrasting effects of CBD on the apoptosis between normal and immortalized glial cells have been reported. The present study investigated the pro-apoptotic effect of CBD on primary microglial cells. CBD induced a time- and concentration-dependent apoptosis in murine primary microglial cells, as evidenced by increase in hypodiploid cells and DNA strand breaks. CBD also caused the loss of mitochondrial membrane potential and the activation of both caspase-8 and -9. Mechanistic studies showed that thiol antioxidants, abnormal-CBD and specific antagonists for vanilloid, CB1 and CB2 receptors did not counteract the CBD-induced apoptosis. In contrast, methyl-β-cyclodextrin (MCD), a lipid raft disruptor, potently attenuated CBD-induced microglial apoptosis and associated signaling events. Moreover, CBD induced lipid raft coalescence and elevated the expression of GM1 ganglioside and caveolin-1, all of which were attenuated by MCD. Collectively, these results suggest that CBD induces a marked pro-apoptotic effect in primary microglia, which is mediated by lipid rafts.
