Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice
Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice
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DOI：
10.1016/s0306-4522(02)00798-4
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Steiner, RA
中科院分区：
文献类型：
--
作者：
Hohmann, JG;Juréus, A;Steiner, RA
为了了解更多关于由于肽类神经递质的慢性过量或缺乏而发生的大脑分子变化，我们研究了遗传操纵神经肽甘丙肽对其同源受体之一甘丙肽受体1表达的影响。首先，我们研究了甘丙肽受体1信使RNA在小鼠前脑中的分布，发现它在许多脑区域中大量表达，包括许多下丘脑和其他与神经内分泌功能相关的前脑区域。甘丙肽受体1信使RNA在小鼠中的分布与大鼠中先前的报道相似，在尾壳核和几个中脑区域中观察到额外的表达。接下来，使用定量原位杂交，我们测量了过表达甘丙肽（甘丙肽转基因）或缺乏功能性甘丙肽基因（甘丙肽敲除）的小鼠大脑中甘丙肽受体1信使RNA的细胞水平。我们报告说，相对于野生型对照，甘丙肽受体1信使RNA的表达增加，在大脑的离散区域甘丙肽转基因小鼠，但消耗甘丙肽/去甲肾上腺素能神经支配下丘脑与神经毒素6-羟基多巴胺没有改变甘丙肽受体1信使RNA的水平。我们还报告了甘丙肽受体1信使RNA的水平在甘丙肽敲除小鼠和野生型小鼠之间没有差异。这些结果表明，同源受体表达的补偿性调整代表了一种机制，通过这种机制，发育中的神经系统试图维持体内平衡，以响应肽能递质的过度表达。然而，在甘丙肽敲除小鼠中甘丙肽受体1信使RNA缺乏显著变化表明，即使在完全不存在配体的情况下，发育编程的受体表达水平也得以维持。(C)2003年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
To learn more about molecular alterations in the brain that occur as a consequence of either the chronic excess or absence of peptide neurotransmitters, we examined the impact of genetically manipulating the neuropeptide galanin on the expression of one of its cognate receptors, galanin receptor 1. First, we examined the distribution of galanin receptor 1 messenger RNA in the mouse forebrain, and found it to be abundantly expressed in many brain regions, including in numerous hypothalamic and other forebrain regions associated with neuroendocrine function. The distribution of galanin receptor 1 messenger RNA in the mouse was similar to previous reports in the rat, with additional expression noted in the caudate putamen and in several midbrain regions. Next, using quantitative in situ hybridization, we measured cellular levels of galanin receptor 1 messenger RNA in the brains of mice that either overexpress galanin (galanin transgenic) or lack a functional galanin gene (galanin knockout). We report that relative to wild-type controls, the expression of galanin receptor 1 messenger RNA was increased in discrete areas of the brain in galanin-transgenic mice, but that depletion of galanin/noradrenergic innervation to the hypothalamus with the neurotoxin 6-hydroxy-dopamine did not alter levels of galanin receptor 1 messenger RNA. We also report that levels of galanin receptor 1 messenger RNA were not different between galanin-knockout and wild-type mice. These results suggest that compensatory adjustments in the expression of cognate receptors represent one mechanism by which the developing nervous system attempts to maintain homeostasis in response to overexpression of a peptidergic transmitter. However, the lack of significant changes in galanin receptor 1 messenger RNA in galanin-knockout mice suggests that developmentally programmed levels of receptor expression are maintained even in the complete absence of ligand. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.