Distribution of Microsomal Prostaglandin E Synthase-1 in the Mouse Brain
Distribution of Microsomal Prostaglandin E Synthase-1 in the Mouse Brain
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DOI：
10.1002/cne.23593
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发表时间：
2014-10-01
影响因子：
2.5
通讯作者：
Blomqvist, Anders
中科院分区：
文献类型：
--
作者：
Eskilsson, Anna;Tachikawa, Masanori;Blomqvist, Anders
先前对大鼠的研究表明，微粒体前列腺素E合成酶-1 （mPGES-1）在也表达诱导型环氧化酶-2的脑血管细胞中被诱导，这表明这些细胞是外周免疫刺激后大脑中PGE(2)水平升高的来源，并与诸如发烧、厌食和应激激素释放等疾病反应有关。然而，尽管大多数关于mPGES-1在这些中枢诱发症状中的功能作用的已知信息是基于对转基因小鼠的研究，但mPGES-1在小鼠大脑中的细胞定位尚未完全确定。在这里，我们使用一种新开发的抗体特异性识别小鼠mPGES-1和细胞特异性标记，我们报告了mPGES-1在小鼠大脑中组成性表达，不仅存在于脑内皮细胞中，而且存在于其他几种细胞类型和结构中，如毛细血管相关周细胞、星形胶质细胞、轻脑膜和脉络膜丛。区域差异在自主神经接力结构如脑后区、皮质下器官、室旁下丘脑核、弓形核和视前区被观察到特别显著的标记。免疫刺激后，mPGES-1在脑内皮细胞中与环氧化酶-2共表达，而在其他mPGES-1阳性细胞中不与环氧化酶-1共表达，而mPGES-1与环氧化酶-1之间无共表达。这些数据表明，PGE(2)或其他mpges -1依赖性产物在小鼠大脑中广泛合成，可能与炎症引起的疾病症状以及其他功能（如血流调节）有关。(C) 2014 Wiley期刊公司
Previous studies in rats have demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1) is induced in brain vascular cells that also express inducible cyclooxygenase-2, suggesting that such cells are the source of the increased PGE(2) levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES-1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES-1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell-specific markers, we report that mPGES-1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary-associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES-1 in brain endothelial cells, but not in other mPGES-1-positive cells, was coexpressed with cyclooxygenase-2, whereas there was no coexpression between mPGES-1 and cyclooxygenase-1. These data imply a widespread synthesis of PGE(2) or other mPGES-1-dependent products in the mouse brain that may be related to inflammation-induced sickness symptom as well as other functions, such as blood flow regulation. (C) 2014 Wiley Periodicals, Inc.