Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity
Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity
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DOI：
10.1152/jn.2002.87.6.2851
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发表时间：
2002-06-01
影响因子：
2.5
通讯作者：
Bazan, NG
中科院分区：
文献类型：
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作者：
Chen, C;Magee, JC;Bazan, NG
环氧合酶（考克斯-1和-2）是在脑中将花生四烯酸（AA）转化为前列腺素（PGs）的关键酶，尽管它们与细胞功能和一些神经系统疾病（包括中风、癫痫和阿尔茨海默病）有关，但其功能意义尚不清楚。最近的证据表明，考克斯-2在突触后树突棘（这是参与突触信号传导的专门结构）中表达，并受突触活动的调节，这意味着考克斯-2参与神经元可塑性。然而，缺乏直接证据。在这里，我们证明，选择性考克斯-2抑制剂显着降低突触后膜兴奋性，反向传播树突状细胞动作电位相关的钙离子内流，和长时程增强（LTP）诱导海马齿状颗粒神经元，而考克斯-1抑制剂是无效的。外源性PGE（2）可有效逆转上述作用，而PGD（2）或PGF（2 α）则不能。我们的结果表明，考克斯-2产生的PGE（2）调节海马穿通通路-齿状回突触的膜兴奋性和长时程突触可塑性。
The functional significance of cyclooxygenases (COX-1 and -2), the key enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in brain, is unclear, although they have been implicated in cellular functions and in some neurologic disorders, including stroke, epilepsy, and Alzheimer's disease. Recent evidence that COX-2 is expressed in postsynaptic dendritic spines (which are specialized structures involved in synaptic signaling) and is regulated by synaptic activity implies participation of COX-2 in neuronal plasticity. However, direct evidence is lacking. Here we demonstrate that selective COX-2 inhibitors significantly reduced postsynaptic membrane excitability, back-propagating dendritic action potential-associated Ca2+ influx, and long-term potentiation (LTP) induction in hippocampal dentate granule neurons, while a COX-1 inhibitor is ineffective. All of these actions were effectively reversed by exogenous application of PGE(2) but not of PGD(2) or PGF(2alpha). Our results indicate that COX-2-generated PGE(2) regulates membrane excitability and long-term synaptic plasticity in hippocampal perforant path-dentate gyrus synapses.