Lafarga M, Berciano M T, Garcia-Segura L M, Andres M A, Carmo-Fonseca M
Department of Anatomy and Cell Biology, Faculty of Medicine, University of Cantabria, Santander, Spain.
J Neurocytol. 1998 Apr;27(4):205-17. doi: 10.1023/a:1006937032068.
Administration of hypertonic NaCl solutions by intraperitoneal injection evokes a transient expression of immediate-early genes in the hypothalamic magnocellular neurons of supraoptic nuclei (SON), which is followed by an upregulation of arginine vasopressin synthesis and a general increase in cellular metabolic activity. Here we have analysed the changes that occur in the nucleus of SON neurons during the period of transient Fos expression after injection of hypertonic saline. Within the first 30 minutes after injection, the nuclei become significantly smaller, contain more condensed chromatin and incorporate less 3H-uridine than the controls. By 12 hours these effects are reverting and at 24 hours the nuclei are already more active than the controls. Additionally, we observe an initial decrease in the number of coiled bodies per nucleus within the first 2 hours, followed by a 3-fold increase at 24 hours after injection. As coiled bodies are transcription-dependent subnuclear 'organelles', these results further support the view that injection of hypertonic saline causes a transient inhibition of nuclear activity. Our data show that SON neurons respond to acute osmotic/stress stimuli first with inhibition and then with activation of gene expression. Importantly, inhibition of transcriptional activity occurs simultaneously with maximal accumulation of Fos protein in the nucleus, raising the possibility that activation of c-fos expression may cause repression of target genes.
通过腹腔注射给予高渗氯化钠溶液,可引起视上核(SON)下丘脑大细胞神经元中即刻早期基因的瞬时表达,随后精氨酸加压素合成上调,细胞代谢活性普遍增加。在此,我们分析了注射高渗盐水后瞬时Fos表达期间SON神经元细胞核中发生的变化。注射后30分钟内,细胞核显著变小,染色质凝聚程度更高,与对照组相比,3H-尿苷掺入量更少。到12小时时,这些效应开始逆转,24小时时细胞核的活性已经高于对照组。此外,我们观察到注射后最初2小时内核仁小体数量每核出现初始下降,随后在24小时时增加3倍。由于核仁小体是转录依赖性的亚核“细胞器”,这些结果进一步支持了注射高渗盐水会导致核活性瞬时抑制的观点。我们的数据表明,SON神经元对急性渗透压/应激刺激的反应先是抑制,然后是基因表达激活。重要的是,转录活性的抑制与Fos蛋白在细胞核中的最大积累同时发生,这增加了c-fos表达激活可能导致靶基因抑制的可能性。