A COMPARISON OF 2 IMMEDIATE-EARLY GENES, C-FOS AND NGFI-B, AS MARKERS FOR FUNCTIONAL ACTIVATION IN STRESS-RELATED NEUROENDOCRINE CIRCUITRY
A COMPARISON OF 2 IMMEDIATE-EARLY GENES, C-FOS AND NGFI-B, AS MARKERS FOR FUNCTIONAL ACTIVATION IN STRESS-RELATED NEUROENDOCRINE CIRCUITRY
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DOI：
10.1523/jneurosci.13-12-05126.1993
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发表时间：
1993-12-01
影响因子：
5.3
通讯作者：
SAWCHENKO, PE
中科院分区：
文献类型：
--
作者：
CHAN, RKW;BROWN, ER;SAWCHENKO, PE
大鼠促肾上腺皮质激素释放因子（CRF）、催产素（OT）和血管加压素（AVP）基因的启动子区含有与NGFI-B（一种结构上与类固醇激素受体超家族相关的立即早期基因）的顺式作用反应元件相似的序列。结合免疫和杂交组织化学方法被用来确定是否挑战，影响CRF，OT，和/或AVP的合成和分泌导致NGFI-B和另一个立即早期基因，c-fos，这是广泛使用的功能激活的神经元的标记物的神经分泌神经元中的表达改变。NGFI-B mRNA被发现在端脑中以组成性的高水平表达，但在未受干扰的对照组的内分泌下丘脑中不表达; c-fos表达的基础水平在整个CNS中均较低。NGFI-B和c-fos mRNA以及Fos蛋白在类似的神经内分泌细胞类型中诱导，以响应急性出血（血容量减少15%）、静脉注射白细胞介素-1 β（IL-1 β; 1.87 μ g/kg）、慢性盐负荷（2%生理盐水维持7天）和急性双侧肾上腺切除术。c-fos mRNA和Fos蛋白在传入通路中很容易被证实，这些通路在三种应激模式中被认为是介导神经内分泌反应的通路;这些通路包括响应于IL-1 β和出血的髓质儿茶酚胺能细胞群，以及响应于盐负荷的终板内衬细胞群。在这些下丘脑外细胞组中可检测到NGFI-B表达的神经元特异性诱导，尽管其敏感性低于揭示下丘脑中NGFI-B诱导或这些相关传入神经中c-fos表达所需的敏感性。这些结果建立NGFI-B作为一个有用的辅助c-fos，揭示突触和/或转录激活的大细胞和小细胞神经分泌系统。这两种标记物在揭示下丘脑外区域功能相关激活方面的敏感性差异，说明了关于在CNS功能电路映射中使用立即早期基因的一般问题。
The promoter regions of the rat corticotropin-releasing factor (CRF), oxytocin (OT), and vasopressin (AVP) genes contain sequences similar to the cis-acting response element identified for NGFI-B, an immediate-early gene structurally related to the steroid hormone receptor superfamily. Combined immuno- and hybridization histochemical approaches were used to determine whether challenges that influence the synthesis and secretion of CRF, OT, and/or AVP result in altered expression in neurosecretory neurons of NGFI-B and another immediate-early gene, c-fos, which is widely used as a marker for functionally activated neurons. NGFI-B mRNA was found to be expressed at constitutively high levels in the telencephalon, but not in the endocrine hypothalamus, of unperturbed controls; basal levels of c-fos expression were uniformly low throughout the CNS. NGFI-B and c-fos mRNAs, and Fos protein, were induced with a similar time course and in similar neuroendocrine cell types in response to acute hypotensive hemorrhage (15% reduction in blood volume), intravenous injection of interleukin-1beta (IL-1beta; 1.87 mug/kg), chronic salt loading (7 d maintenance on 2% saline), and acute bilateral adrenalectomy. c-fos mRNA and Fos protein were readily demonstrable in afferent pathways that have been implicated as mediating the neuroendocrine responses in the three stress paradigms; these include medullary catecholaminergic cell groups in response to IL-1beta and hemorrhage, and cell groups lining the lamina terminalis in response to salt loading. Challenge-specific induction of NGFI-B expression was detectable in these extrahypothalamic cell groups, though with a lesser sensitivity than that required to reveal NGFI-B induction in the hypothalamus, or c-fos expression in these related afferents. These results establish NGFI-B as a useful adjunct to c-fos, for revealing synaptic and/or transcriptional activation in the magno- and parvocellular neurosecretory systems. Differences in the sensitivity of the two markers in revealing functionally related activation in extrahypothalamic regions speak to general issues concerning the use of immediate-early genes in mapping functional circuitry in the CNS.