Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1

• Published in: The Journal of biological chemistry 2000-08, Vol.275 (34), p.26252-26258
• Main Authors: Vereker, E, Campbell, V, Roche, E, McEntee, E, Lynch, M A
• Format: Article
• Language: English
• Subjects: Animals; Caspase 1 - metabolism; Culture Techniques; Cytochrome c Group - metabolism; Dentate Gyrus - drug effects; Dentate Gyrus - enzymology; Enzyme Activation; Hippocampus - drug effects; Hippocampus - metabolism; Interleukin-1 - metabolism; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides - pharmacology; Long-Term Potentiation - drug effects; Male; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Rats; Rats, Wistar
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M002226200

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-1β (IL-1β) concentration. We report that intraperitoneal injection of lipopolysaccharide increased hippocampal caspase-1 activity and IL-1β concentration; these changes were associated with increased activity of the stress-activated kinase c-Jun NH 2 -terminal kinase, decreased glutamate release, and impaired long term potentiation. The degenerative changes in hippocampus and entorhinal cortical neurones were consistent with apoptosis because translocation of cytochrome c and poly(ADP-ribose) polymerase cleavage were increased. Inhibition of caspase-1 blocked these changes, suggesting that IL-1β mediated the lipopolysaccharide-induced changes.