Vasopressin and corticotropin-releasing hormone gene responses to novel stress in rats adapted to repeated restraint
Vasopressin and corticotropin-releasing hormone gene responses to novel stress in rats adapted to repeated restraint
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DOI：
10.1210/en.140.8.3623
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发表时间：
1999-08-01
期刊：
影响因子：
4.8
通讯作者：
Aguilera, G
中科院分区：
文献类型：
--
作者：
Ma, XM;Lightman, SL;Aguilera, G
下丘脑室旁核（PVN）的应激反应神经元具有功能可塑性，能适应重复束缚（RR）应激。为了研究神经元对同型应激的适应是否也影响其对异型应激的反应，我们使用内含子和外显子探针原位杂交来测量在ip高渗盐水注射（ipHS）异型应激后对照和RR大鼠PVN中CRH和加压素（VP）的初级转录物（hnRNA）和信使RNA（mRNA）水平。两个星期的日常约束钝化血浆皮质酮和小细胞CRH，但不是VP，转录反应进一步约束事件。IPHS增加循环皮质酮在两组中，但水平较高的RR大鼠。CRH hnRNA在15分钟内增加，并在1小时内恢复到基线水平。CRH mRNA在两组中增加较慢，在2小时达到峰值，RR大鼠在此时表现出更大的反应。小细胞VP hnRNA在幼稚大鼠ipHS后2 h达到峰值，但在RR大鼠中更快（1 h）且达到更高水平。在两组中，表达VP hnRNA的小细胞神经元的数量在ipHS后增加约5倍。RR大鼠基础VP mRNA水平和表达VP mRNA的小细胞数量增加。ipHS和幼稚大鼠均显示ipHS后VP mRNA转录增加，RR大鼠在2和4 h显示更高水平。在PVN和视上核的大细胞显示VP hnRNA在15分钟内增加。数据表明VP反应在小细胞神经元的控制和RR大鼠，而深刻的抑制CRH转录是选择性的同型应激与CRH反应的异型应力保存或增加。
Stress-responsive neurons of the hypothalamic paraventricular nucleus (PVN) show functional plasticity and adapt to repeated restraint (RR) stress. To investigate whether neuronal adaptation to the homotypic stress also affects their response to a heterotypic stressor, we used in situ hybridization with intronic and exonic probes to measure primary transcript (hnRNA) and messenger RNA (mRNA) levels for CRH and vasopressin (VP) in the PVN of control and RR rats after the heterotypic stress of ip hypertonic saline injection (ipHS). Two weeks of daily restraint blunted plasma corticosterone and parvocellular CRH, but not VP, transcript responses to a further restraint episode. IpHS increased circulating corticosterone in both groups, but levels were higher in RR rats. CRH hnRNA increased within 15 min and returned to baseline by 1 h in both naive and RR rats. CRH mRNA increased more slowly in both groups, peaking at 2 h, with RR rats showing greater responses at this time. Parvocellular VP hnRNA reached a peak 2 h after ipHS in naive rats, but more rapidly (1 h) and to higher levels in RR rats. The number of parvocellular neurons expressing VP hnRNA increased approximately 5-fold after ipHS in both groups. Basal VP mRNA levels and the number of parvocellular cells expressing VP mRNA were elevated in RR rats. Both ipHS and naive rats showed an increase in VP mRNA transcripts after ipHS, with RR rats showing greater levels at 2 and 4 h. Magnocellular cells in both PVN and supraoptic nuclei showed increases in VP hnRNA within 15 min. The data demonstrate VP responses in parvocellular neurons of both control and RR rats, whereas profound inhibition of CRH transcription is selective for the homotypic stressor with CRH responsiveness to the heterotypic stress preserved or increased.