Cowley T R, Fahey B, O'Mara S M
Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Eur J Neurosci. 2008 Jun;27(11):2999-3008. doi: 10.1111/j.1460-9568.2008.06251.x. Epub 2008 Jun 6.
The objectives of this research were to investigate the role played by the enzyme cyclooxygenase (COX) in learning and memory, synaptic plasticity and synaptic transmission in the rat brain in vivo. Male Wistar rats were treated with isoform-selective inhibitors for COX-1 and COX-2, either chronically and tested in the watermaze or acutely before electrophysiological recordings were made. We found a significant impairment in acquisition of the watermaze with inhibition of COX-2. Furthermore, we found COX-2 but not COX-1 inhibition significantly blocked long-term potentiation (LTP) induction but had no effect on already established LTP. Moreover, exogenous replacement of the main metabolite of COX-2 activity, PGE(2), was sufficient to restore LTP induction and for normal downstream signalling to ensue, namely extracellular signalling-regulated kinase (ERK)-phosphorylation and c-FOS expression. We conclude that endogenous basal levels of PGE(2) resulting from COX-2 but not COX-1 activity are necessary for synaptic plasticity and memory acquisition.
本研究的目的是调查环氧化酶（COX）在大鼠大脑体内学习与记忆、突触可塑性和突触传递中所起的作用。雄性Wistar大鼠长期接受COX - 1和COX - 2同工型选择性抑制剂治疗，并在水迷宫中进行测试，或者在进行电生理记录之前急性给药。我们发现，抑制COX - 2会导致水迷宫学习能力显著受损。此外，我们发现抑制COX - 2而非COX - 1会显著阻断长时程增强（LTP）的诱导，但对已建立的LTP没有影响。此外，外源性补充COX - 2活性的主要代谢产物前列腺素E2（PGE2）足以恢复LTP的诱导并确保正常的下游信号传导，即细胞外信号调节激酶（ERK）磷酸化和c - FOS表达。我们得出结论，由COX - 2而非COX - 1活性产生的内源性基础水平的PGE2对于突触可塑性和记忆获取是必要的。
