Chan R K, Sawchenko P E
Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Neuroscience. 1995 May;66(2):377-90. doi: 10.1016/0306-4522(94)00600-a.
Medullary catecholamine cell groups are involved in multiple modes of cardiovascular regulation and display indices of functional activation, including widespread c-fos expression, in response to hypotensive hemorrhage. Assessments of the impact of such challenges on transmitter-related gene expression are complicated by the biochemical and connectional heterogeneity that characterize these cell groups. Quantitative hybridization histochemical methods were used to follow the effects of 15% hemorrhage on levels of messenger RNA encoding tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in medullary aminergic neurons; concurrent staining for nuclear Fos-immunoreactivity permitted comparisons between cells that ostensibly were and were not targeted by the challenge. Increased levels of tyrosine hydroxylase messenger RNA were detected in Fos-immunoreactive neurons in all cell groups examined. Mean maximal increases ranged between 133 and 192% of control values, and were attained within 0.5-1 h post-hemorrhage in noradrenergic (A1 and A2) cell groups, and at 2 h in adrenergic ones (C1, C2, and C2d or dorsal strip). By 4 h after the challenge, tyrosine hydroxylase messenger RNA levels in Fos-immunoreactive neurons in all cell groups had returned to control values. By contrast, tyrosine hydroxylase messenger RNA in non-Fos-immunoreactive cells either did not change significantly over the course of the experiment (C2 and C2d), or showed a rapid and transient increase, whose magnitude tended to be less than that seen in Fos-immunoreactive cells. c-fos messenger RNA was prominently induced in catecholaminergic neurons in each of the medullary cell groups examined at 0.5 h after hemorrhage, suggesting that the early tyrosine hydroxylase messenger RNA response to hemorrhage in non-Fos-immunoreactive cells preceded the capacity of responsive neurons to manifest detectable Fos protein expression. These findings indicate that hemorrhage up-regulates tyrosine hydroxylase messenger RNA levels in medullary catecholaminergic cell groups which have access to adaptive neuroendocrine and/or autonomic control systems. The approach employed here should prove of general utility in assessing the impact of environmental events on messenger RNA expression in connectionally heterogeneous cell groups that share a common biochemical phenotype.
髓质儿茶酚胺细胞群参与多种心血管调节模式，并在低血压性出血时表现出功能激活指标，包括广泛的c-fos表达。这些细胞群具有生化和连接异质性，这使得评估此类应激对递质相关基因表达的影响变得复杂。采用定量杂交组织化学方法，观察15%出血对髓质胺能神经元中编码酪氨酸羟化酶（儿茶酚胺生物合成中的限速酶）的信使RNA水平的影响；同时对核Fos免疫反应性进行染色，以便比较表面上受到和未受到应激影响的细胞。在所检查的所有细胞群中，Fos免疫反应性神经元中酪氨酸羟化酶信使RNA水平均升高。平均最大增幅在对照值的133%至192%之间，去甲肾上腺素能（A1和A2）细胞群在出血后0.5 - 1小时达到，而肾上腺素能细胞群（C1、C2和C2d或背侧条带）在2小时达到。应激后4小时，所有细胞群中Fos免疫反应性神经元中的酪氨酸羟化酶信使RNA水平已恢复到对照值。相比之下，非Fos免疫反应性细胞中的酪氨酸羟化酶信使RNA在实验过程中要么没有显著变化（C2和C2d），要么显示出快速且短暂的增加，其幅度往往小于Fos免疫反应性细胞中的增加幅度。出血后0.5小时，在所检查的每个髓质细胞群的儿茶酚胺能神经元中均显著诱导了c-fos信使RNA，这表明非Fos免疫反应性细胞中酪氨酸羟化酶信使RNA对出血的早期反应先于反应性神经元表现出可检测到的Fos蛋白表达的能力。这些发现表明，出血上调了髓质儿茶酚胺能细胞群中酪氨酸羟化酶信使RNA水平，这些细胞群可利用适应性神经内分泌和/或自主控制系统。本文采用的方法在评估环境事件对具有共同生化表型的连接异质性细胞群中信使RNA表达的影响方面应具有普遍实用性。
