Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation
Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation
复制标题
DOI：
10.1016/j.neuropharm.2009.06.019
复制
发表时间：
2010-01-01
影响因子：
4.7
通讯作者：
Gundlach, Andrew L.
中科院分区：
文献类型：
--
作者：
Banerjee, Avantika;Shen, Pei-Juan;Gundlach, Andrew L.
松弛素-3（Relaxin-3，RLX 3）是新近发现的松弛素肽家族成员，其特征在于其在脑桥未定核（NI）的GABA投射神经元中的富集表达，该神经元被认为参与了涉及行为激活和应激反应的前脑神经回路。在这方面，NI神经元大量表达促肾上腺皮质激素释放因子-1受体（CRF 1）;中枢CRF给药激活NI中的c-fos表达;据报道，各种应激源都会增加NI神经元的活性。在研究中，以确定是否一个特定的神经源性应激会激活RLX 3的表达，我们评估了重复强迫游泳（RFS）对RLX 3的mRNA和heterozygous（hn）RNA水平的影响，在大鼠NI的外显子和内含子定向的寡核苷酸探针，分别通过原位杂交组织化学。大鼠暴露于RFS（23 ℃下10分钟，间隔2 - 4小时），在第二次游泳后30-60分钟显著增加NI中的RLX 3 mRNA水平，然后在2-4小时内逐渐恢复到基础水平，而RLX 3 hnRNA水平在RFS后60-120分钟显著上调，用CRF 1拮抗剂antalarmin（20 mg/kg，i. p.）在第二次游泳前30分钟，减弱了应激诱导的对RLX 3转录物的影响。NI神经元中RLX 3免疫染色的相对水平在游泳后3小时出现升高，但在更早的时间点（30-60分钟）没有。这些结果表明，急性应激诱导的CRF分泌可以通过激活NI神经元上的CRF 1快速改变RLX 3基因转录。更一般地说，这些研究支持RLX 3神经网络在大鼠对神经源性应激源的正常神经和生理反应中的作用。(C)2009爱思唯尔有限公司版权所有。
Relaxin-3 (RLX3), a newly identified member of the relaxin peptide family, is distinguished by its enriched expression in GABA projection neurons of the pontine nucleus incertus (NI), which are postulated to participate in forebrain neural circuits involved in behavioural activation and stress responses. In this regard, corticotrophin-releasing factor-1 receptor (CRF1) is abundantly expressed by NI neurons; central CRF administration activates c-fos expression in NI; and various stressors have been reported to increase NI neuron activity. In studies to determine whether a specific neurogenic stressor would activate RLX3 expression, we assessed the effect of a repeated forced swim (RFS) on levels of RLX3 mRNA and heteronuclear (hn) RNA in rat NI by in situ hybridization histochemistry of exon- and intron-directed oligonucleotide probes, respectively. Exposure of rats to an RFS (10 min at 23 degrees C, 24 h apart), markedly increased RLX3 mRNA levels in NI at 30-60 min after the second swim, before a gradual return to basal levels over 2-4 h, while RLX3 hnRNA levels were significantly up-regulated at 60-120 min post-RFS, following a transient decrease at 30 min. Systemic treatment of rats with a CRF1 antagonist, antalarmin (20 mg/kg, i.p.) 30 min prior to the second swim, blunted the stress-induced effects on RLX3 transcripts. Relative levels of RLX3-immunostaining in NI neurons appeared elevated at 3 h post-swim, but not at earlier time points (30-60 min). These results suggest that acute stress-induced CRF secretion can rapidly alter RLX3 gene transcription by activation of CRF1 present on NI neurons. More generally, these studies support a role for RLX3 neural networks in the normal neural and physiological response to neurogenic stressors in the rat. (C) 2009 Elsevier Ltd. All rights reserved.