Yamagata K, Andreasson K I, Kaufmann W E, Barnes C A, Worley P F
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185.
Neuron. 1993 Aug;11(2):371-86. doi: 10.1016/0896-6273(93)90192-t.
Prostaglandins play important and diverse roles in the CNS. The first step in prostaglandin synthesis involves enzymatic oxidation of arachidonic acid, which is catalyzed by prostaglandin H(PGH) synthase, also referred to as cyclooxygenase. We have cloned an inducible form of this enzyme from rat brain that is nearly identical to a murine, mitogen-inducible cyclooxygenase identified from fibroblasts. Our studies indicate that this gene, here termed COX-2, is expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus. Neuronal expression is rapidly and transiently induced by seizures or NMDA-dependent synaptic activity. No expression is detected in glia or vascular endothelial cells. Basal expression of COX-2 appears to be regulated by natural synaptic activity in the developing and adult brain. Both basal and induced expression of COX-2 are inhibited by glucocorticoids, consistent with COX-2 regulation in peripheral tissues. Our studies indicate that COX-2 expression may be important in regulating prostaglandin signaling in brain. The marked inducibility in neurons by synaptic stimuli suggests a role in activity-dependent plasticity.
前列腺素在中枢神经系统中发挥着重要且多样的作用。前列腺素合成的第一步涉及花生四烯酸的酶促氧化，这一过程由前列腺素H（PGH）合酶催化，该酶也被称为环氧化酶。我们已从大鼠脑中克隆出这种酶的一种诱导型，它与从成纤维细胞中鉴定出的小鼠促分裂原诱导型环氧化酶几乎相同。我们的研究表明，这个基因，在这里被称为COX - 2，在前脑的离散神经元群体中表达，并在皮层和海马体中富集。癫痫发作或NMDA依赖的突触活动可迅速且短暂地诱导神经元表达。在胶质细胞或血管内皮细胞中未检测到表达。COX - 2的基础表达似乎受发育中和成年大脑中自然突触活动的调节。COX - 2的基础表达和诱导表达均受到糖皮质激素的抑制，这与外周组织中COX - 2的调节一致。我们的研究表明，COX - 2的表达可能在调节大脑中的前列腺素信号传导方面很重要。突触刺激在神经元中显著的诱导性表明其在活动依赖性可塑性中发挥作用。
