COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex

COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex
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DOI:
10.1073/pnas.93.6.2317
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发表时间:
1996-03-19
影响因子:
11.1
通讯作者:
Isakson, P
Isakson, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kaufmann, WE;Worley, PF;Isakson, P

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中枢神经系统的出生后发育和成年功能依赖于神经元响应神经活动而实现特定性质的长期变化的能力。已经证明这种神经元响应与一组调控基因的表达密切相关,所述调控基因包括转录因子以及可以直接修饰细胞信号传导的分子,假设这些蛋白质在活性依赖性反应中起作用。以前,我们描述了脑中前列腺素合酶/环氧合酶的诱导型,称为考克斯-2,考克斯-2是前列腺素类合成的限速酶,其表达在发育和成年前脑中通过生理性突触活动快速调节,在这里,我们证明,考克斯-2免疫反应性选择性地表达在一个亚群的兴奋性神经元在新的和异体皮质,海马,杏仁核和区室化的树突分支,此外,考克斯-2免疫反应性存在于树突棘,这是专门的结构参与突触信号,树突中考克斯-2表达的发育概况遵循公知的组织发生梯度,并且与活性依赖性突触重塑的关键时期一致。这些结果表明,考克斯-2及其可扩散的前列腺素类产物,可能在皮层和相关结构中兴奋性神经元的突触后信号传导中起作用。
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 responses, 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.