Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation.
Peripheral administration of lipopolysaccharide (LPS), a potent bacterial endotoxin, can cause a variety of central effects, including production of cytokines and cyclooxygenases in the brain, as well as peripheral increases in corticosterone. These, in turn, may contribute to neuroimmune-induced neurocognitive deficits. We show here LPS causes deficits in hippocampal-dependent spatial learning in the water maze but that treatment with ibuprofen, a broad-spectrum cyclooxygenase inhibitor, reverses the deficits induced in spatial learning by LPS. We also show that LPS causes an impairment in the induction of long-term potentiation in the dentate gyrus in vivo, a major contemporary model of learning and memory. No differences were found in corticosterone levels in trunk blood but we find a decrease in brain-derived neurotrophic factor (BDNF) expression in LPS group compared to saline controls. Paradoxically compared to the behavioral findings treatment with ibuprofen does not attenuate the LPS-induced impairment in LTP or BDNF concentration in tetanized tissue.
Shaw
Kendra N
KN
Department of Psychology and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Commins
Sean
S
O'Mara
Shane M
SM
D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000503:physiopathology; D007052:Ibuprofen / Q000494:pharmacology; D007859:Learning Disabilities / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D008070:Lipopolysaccharides; D011451:Prostaglandin-Endoperoxide Synthases; D003345:Corticosterone; D007052:Ibuprofen