A role for inflammatory mediators in the IL-18 mediated attenuation of UP in the rat dentate gyrus
A role for inflammatory mediators in the IL-18 mediated attenuation of UP in the rat dentate gyrus
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DOI：
10.1016/j.neuropharm.2007.03.006
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
O'Connor, J. J.
中科院分区：
文献类型：
--
作者：
Cumiskey, D.;Curran, B. P.;O'Connor, J. J.
已知促炎细胞因子在与认知缺陷相关的几种病理状况中升高。我们以前已经证明，白细胞介素-18（IL-18）抑制长时程增强（LTP）在体外齿状回。在这项研究中，我们已经检查了炎症介质考克斯-2和诱导型一氧化氮合酶在IL-18介导的抑制LTR的参与。抗炎性过氧化物酶体增殖物激活受体γ激动剂的作用也进行了研究。我们报道，IL-18对UP的损害通过预先应用考克斯-2抑制剂SC-236和iNOS抑制剂1400 W而显著减弱。这些药物对齿状回的成对脉冲抑制没有影响。此外，应用PPAR γ激动剂环格列酮也减弱了IL-18介导的LTR抑制。我们讨论了p38 MAP激酶在这些作用中的作用。本研究为炎症介质参与IL-18介导的体外大鼠齿状回LTP抑制提供了新的证据。(c)2007爱思唯尔有限公司保留所有权利。
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 LTR The effect of an anti-inflammatory PPAR gamma agonist was also investigated. We report that the impairment of UP 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 PPAR gamma agonist ciglitazone also attenuated IL-18-mediated inhibition of LTR 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. (c) 2007 Elsevier Ltd. All rights reserved.