Kaufmann W E, Worley P F, Pegg J, Bremer M, Isakson P
Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2317-21. doi: 10.1073/pnas.93.6.2317.
Postnatal development and adult function of the central nervous system are dependent on the capacity of neurons to effect long-term changes of specific properties in response to neural activity. This neuronal response has been demonstrated to be tightly correlated with the expression of a set of regulatory genes which include transcription factors as well as molecules that can directly modify cellular signaling. It is hypothesized that these proteins play a role in activity-dependent response. Previously, we described the expression and regulation in brain of an inducible form of prostaglandin synthase/cyclooxygenase, termed COX-2. COX-2 is a rate-limiting enzyme in prostanoid synthesis and its expression is rapidly regulated in developing and adult forebrain by physiological synaptic activity. Here we demonstrate that COX-2 immunoreactivity is selectively expressed in a subpopulation of excitatory neurons in neo-and allocortices, hippocampus, and amygdala and is compartmentalized to dendritic arborizations. Moreover, COX-2 immunoreactivity is present in dendritic spines, which are specialized structures involved in synaptic signaling. The developmental profile of COX-2 expression in dendrites follows well known histogenetic gradients and coincides with the critical period for activity-dependent synaptic remodeling. These results suggest that COX-2, and its diffusible prostanoid products, may play a role in postsynaptic signaling of excitatory neurons in cortex and associated structures.
中枢神经系统的产后发育及成年后的功能取决于神经元响应神经活动而实现特定特性长期改变的能力。这种神经元反应已被证明与一组调控基因的表达紧密相关，这些基因包括转录因子以及能够直接修饰细胞信号传导的分子。据推测，这些蛋白质在依赖活动的反应中发挥作用。此前，我们描述了一种诱导型前列腺素合酶/环氧化酶（称为COX-2）在脑中的表达及调控。COX-2是前列腺素合成中的限速酶，其表达在发育中的和成年前脑可被生理突触活动快速调控。在此我们证明，COX-2免疫反应性在新皮质、旧皮质、海马体和杏仁核的兴奋性神经元亚群中选择性表达，并定位于树突分支。此外，COX-2免疫反应性存在于树突棘中，树突棘是参与突触信号传导的特殊结构。COX-2在树突中表达的发育情况遵循众所周知的组织发生梯度，并与依赖活动的突触重塑关键期一致。这些结果表明，COX-2及其可扩散的前列腺素产物可能在皮质及相关结构中兴奋性神经元的突触后信号传导中发挥作用。
