sc-236 and ciglitazone

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.

Topics: Animals; Cyclooxygenase 2; Dentate Gyrus; Dose-Response Relationship, Radiation; Electric Stimulation; Enzyme Inhibitors; Gene Expression Regulation; Imines; In Vitro Techniques; Interleukin-18; Long-Term Potentiation; Neural Inhibition; Neurons; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Patch-Clamp Techniques; Pyrazoles; Rats; Sulfonamides; Thiazolidinediones