A role for inflammatory mediators in the IL-18 mediated attenuation of LTP in the rat dentate gyrus.
Pro-inflammatory cytokines are known to be elevated in several pathological conditions that are associated with deficits in cognition. We have previously demonstrated that interleukin-18 (IL-18) inhibits long-term potentiation (LTP) in the dentate gyrus in vitro. In this study we have examined the involvement of the inflammatory mediators COX-2 and iNOS in IL-18-mediated inhibition of LTP. The effect of an anti-inflammatory PPARgamma agonist was also investigated. We report that the impairment of LTP by IL-18 is significantly attenuated by prior application of the COX-2 inhibitor, SC-236 and the iNOS inhibitor 1400W. These agents had no effect on paired pulse depression in the dentate gyrus. Furthermore, application of the PPARgamma agonist ciglitazone also attenuated IL-18-mediated inhibition of LTP. We discuss a role for p38 MAP kinase in these effects. This study provides novel evidence for the involvement of inflammatory mediators in IL-18-mediated inhibition of LTP in the rat dentate gyrus in vitro.
Cumiskey
D
D
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular & Biomedical Research, Belfield, Dublin 4, Ireland.
Curran
B P
BP
Herron
C E
CE
O'Connor
J J
JJ
D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D020382:Interleukin-18 / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096926:Benzenesulfonamides
D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors; D007097:Imines; D020382:Interleukin-18; D052247:Nitric Oxide Synthase Type II; D011720:Pyrazoles; D013449:Sulfonamides; D045162:Thiazolidinediones; D048051:p38 Mitogen-Activated Protein Kinases; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; C039671:ciglitazone