期刊
NEUROPHARMACOLOGY
卷 44, 期 3, 页码 374-380出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(02)00375-1
关键词
LTD; LTP; p38 MAPK; COX-2; NS398; dentate gyrus
Long-term potentiation (LTP) and long-term depression (LTD) are two forms of activity-dependent synaptic plasticity that are thought to be involved in learning and memory. Evidence has shown that cyclooxygenase-2 (COX-2), an enzyme that converts arachidonic acid to prostaglandins, is expressed in postsynaptic dendritic spines and is regulated by synaptic activity. COX-2 inhibition has been shown to directly attenuate LTP in the dentate gyrus of the hippocampus. Also recently the p38 MAP kinase cascade, a pathway utilised by cells for COX-2 expression, has been implicated in LTD induction in the CA1 region of the hippocampus. Here we demonstrate for the first time a direct role for COX-2 and p38 MAP kinase in LTD and confirm the inhibitory role of COX-2 in UP in the rat dentate gyrus. Perfusion of the COX-2 inhibitor NS-398 (1 muM) 60 min before tetanic stimulation resulted in an attenuation of LTD (84 +/- 5%, n = 5 compared to controls of 57 +/- 7%, n = 6, P < 0.05). Prolonged exposure (2 h) to NS-398 (1 muM) resulted in a significant reduction in UP (71 +/- 8%, n = 5, P < 0.01 compared to controls of 170 +/- 11%, n = 5 at 60 min post HFS). The p38 MAPK inhibitor, SB220025 (250 nM) significantly attenuated LTD (88 5%, n 7; P < 0.01 compared to vehicle controls at 60 min, 56 5%, n = 6) but had no significant effect on LTP. Both NS-398 and SB220025 had no significant effect on the isolated NMDA-mediated EPSP. These data demonstrate a role for COX-2 and p38 MAPK in LTD in the dentate gyrus in vitro that is independent of NMDA receptor activation. (C) 2003 Elsevier Science Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据