Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling

Acrylamide is a chemical used in various industries and a product following high-temperature cooking of vegetables containing asparagine. Environmental or dietary exposure to acrylamide could impair cognitive function because of its neurotoxicity. Using rat hippocampal slices, we tested whether acrylamide alters induction of long-term potentiation (LTP), a cellular model of learning and memory. We hypothesized that acrylamide impairs cognitive function via activation of pro-inflammatory cytokines because robust upregulation of NLRP3 inflammasome has been reported. Although acrylamide up to 3 mM did not alter basal synaptic transmission, incubation with 10 μM or acute administration of 100 μM acrylamide inhibited induction of LTP. Inhibitors of toll-like receptor 4 (TLR4), and minocycline, an inhibitor of microglial activation, overcame the effects of acrylamide on LTP induction. Furthermore, we observed that acrylamide failed to inhibit LTP after administration of MCC950, an inhibitor of NLRP3, or in the presence of Interleukin-1 receptor antagonist (IL-1Ra). We also found that in vivo acrylamide injection transiently impaired body weight gain and impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by MCC950. These results indicate that cognitive impairment by acrylamide is mediated by mechanisms involving microglia and release of cytokines via NLRP3 activation.