Rossie Sandra, Jayachandran Hemalatha, Meisel Robert L
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Brain Res. 2006 Sep 21;1111(1):1-11. doi: 10.1016/j.brainres.2006.06.106. Epub 2006 Aug 8.
Glucocorticoid receptors are widely expressed in brain, where they are thought to play a role in controlling neurogenesis and to mediate many of the central nervous system effects of stress. In non-neuronal cells, protein phosphatase 5 (PP5) has been found in complexes with heat shock protein 90 and glucocorticoid receptors and may be a negative modulator of glucocorticoid receptor function. In the present study, we used co-immunofluorescence analysis to examine whether PP5 and glucocorticoid receptors are co-expressed at the cellular level in rat brain. In several regions containing major populations of glucocorticoid receptor expressing neurons, PP5 and glucocorticoid receptors were co-localized at the cellular level. These include pyramidal cells of the hippocampal CA1 and CA2 regions and dentate gyrus granule cells, cerebellar Purkinje neurons, cortical pyramidal neurons, neurons of the central nucleus of the amygdala and parvocellular neurons of the hypothalamic paraventricular nucleus. There are also neuronal populations that are stained strongly for glucocorticoid receptors, such as cerebellar granule cells, where PP5 is either absent or below detection limits. Likewise, numerous neuronal populations contain PP5, but not glucocorticoid receptors. Whereas glucocorticoid receptors are expressed in both neurons and glial cells throughout the brain, PP5 appears to be primarily expressed in neurons. These studies suggest that glucocorticoid receptors may be differentially regulated by phosphatase action in different populations of central nervous system cells. Co-localization of PP5 and glucocorticoid receptors in brain regions involved in feedback control of the hypothalamus-pituitary-adrenal axis suggests that PP5 may be an important modulator of glucocorticoid receptor responses in this pathway.
糖皮质激素受体在大脑中广泛表达，人们认为它们在控制神经发生以及介导应激对中枢神经系统的许多影响方面发挥作用。在非神经元细胞中，已发现蛋白磷酸酶5（PP5）与热休克蛋白90和糖皮质激素受体形成复合物，并且可能是糖皮质激素受体功能的负调节因子。在本研究中，我们使用共免疫荧光分析来检查PP5和糖皮质激素受体在大鼠大脑的细胞水平上是否共表达。在几个含有主要糖皮质激素受体表达神经元群体的区域中，PP5和糖皮质激素受体在细胞水平上共定位。这些区域包括海马CA1和CA2区的锥体细胞、齿状回颗粒细胞、小脑浦肯野神经元、皮质锥体细胞、杏仁核中央核的神经元以及下丘脑室旁核的小细胞神经元。也有一些神经元群体对糖皮质激素受体染色强烈，如小脑颗粒细胞，其中PP5不存在或低于检测限。同样，许多神经元群体含有PP5，但不含糖皮质激素受体。虽然糖皮质激素受体在整个大脑的神经元和胶质细胞中均有表达，但PP5似乎主要在神经元中表达。这些研究表明，糖皮质激素受体可能在中枢神经系统不同细胞群体中受到磷酸酶作用的差异调节。PP5和糖皮质激素受体在下丘脑-垂体-肾上腺轴反馈控制相关脑区中的共定位表明，PP5可能是该途径中糖皮质激素受体反应的重要调节因子。
