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-1beta (IL-1beta) concentration. We report that intraperitoneal injection of lipopolysaccharide increased hippocampal caspase-1 activity and IL-1beta 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-1beta mediated the lipopolysaccharide-induced changes.
Vereker
E
E
Physiology Department, Trinity College, Dublin 2, Ireland.
Campbell
V
V
Roche
E
E
McEntee
E
E
Lynch
M A
MA
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D046508:Culture Techniques; D003574:Cytochrome c Group / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D003574:Cytochrome c Group; D007375:Interleukin-1; D008070:Lipopolysaccharides; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020170:Caspase 1