A role for inflammatory mediators in the IL-18 mediated attenuation of LTP in the rat dentate gyrus

• Published in: Neuropharmacology 2007-06, Vol.52 (8), p.1616-1623
• Main Authors: Cumiskey, D., Curran, B.P., Herron, C.E., O'Connor, J.J.
• Format: Article
• Language: English
• Subjects: Animals; COX-2; Cyclooxygenase 2 - physiology; Dentate Gyrus - cytology; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Enzyme Inhibitors - pharmacology; Gene Expression Regulation - drug effects; Imines - pharmacology; In Vitro Techniques; iNOS; Interleukin-18; Interleukin-18 - pharmacology; Long-term potentiation; Long-Term Potentiation - drug effects; Neural Inhibition - drug effects; Neurons - drug effects; Nitric Oxide Synthase Type II - physiology; p38 Mitogen-Activated Protein Kinases - metabolism; Patch-Clamp Techniques - methods; PPARγ; Pyrazoles - pharmacology; Rats; Sulfonamides - pharmacology; Thiazolidinediones - pharmacology
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2007.03.006

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 PPARγ 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 PPARγ 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.