Lipopolysaccharide inhibits long term potentiation in the rat dentate gyrus by activating caspase-1

Lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, may be responsible for at least some of the pathophysiological sequelae of bacterial infections, probably by inducing an increase in interleukin-1 be ta (IL-1 beta) concentration. We report that intraperitoneal injection of l ipopolysaccharide increased hippocampal caspase-1 activity and IL-1 beta co ncentration; these changes were associated with increased activity of the s tress-activated kinase c-Jun NH2-terminal kinase, decreased glutamate relea se, and impaired long term potentiation. The degenerative changes in hippoc ampus and entorhinal cortical neurones were consistent with apoptosis becau se translocation of cyto chrome c and poly(ADP-ribose) polymerase cleavage were increased. Inhibition of caspase-1 blocked these changes, suggesting t hat IL-1 beta mediated the lipopolysaccharide-induced changes.