Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice
Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice
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DOI：
10.1016/j.neuroscience.2005.01.068
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Mufson, EJ
中科院分区：
文献类型：
--
作者：
He, B;Counts, SE;Mufson, EJ
神经肽甘丙肽（GAL）的功能相互作用通过其与三种G蛋白偶联受体亚型（GALR）1、GALR 2和GALR 3）的结合而发生。先前，我们证明了甘丙肽转基因（GAL-tg）小鼠海马CA 1区和离散下丘脑核GALR 1 mRNA表达增加。这一观察结果表明，在面对慢性GAL暴露时，同源受体发生了代偿性调整。为了评估GAL过表达小鼠前脑中GALR 2和GALR 3的分子改变，我们进行了互补定量实时PCR（qPCR），原位杂交，和免疫组织化学在选择前脑区域的GAL-tg小鼠，以表征GAL mRNA和肽表达的神经元分布和幅度，以及遗传操纵神经肽GAL对GALR 2和GALR 3表达的影响受体。我们发现GAL-tg小鼠在额叶皮质、后皮质、海马、隔斜角带复合体、杏仁核、梨状皮质和嗅球中显示GAL mRNA和肽的显著增加。此外，有证据表明，神经元GAL在前脑边缘区域（包括梨状皮质、内嗅皮质和杏仁核）中异位表达，该区域介导认知和情感行为。有趣的是，区域qPCR分析未能揭示GAL-tg小鼠中GALR 2或GALR 3表达的任何变化，这表明与GALR 1相反，这些受体基因不受配体介导的调控。GAL-tg小鼠模型可能为研究GAL配体-受体关系及其在正常认知和情感功能以及神经系统疾病发作中的作用提供有用的工具。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The functional interactions of the neuropeptide galanin (GAL) occur through its binding to three G protein-coupled receptor subtypes: galanin receptor (GALR) 1, GALR2 and GALR3. Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice. This observation suggested a compensatory adjustment in cognate receptors in the face of chronic GAL exposure. To evaluate the molecular alterations to GALR2 and GALR3 in the forebrain of GAL overexpressing mice, we performed complementary quantitative, real-time PCR (qPCR), in situ hybridization, and immunohistochemistry in select forebrain regions of GAL-tg mice to characterize the neuronal distribution and magnitude of GAL mRNA and peptide expression and the consequences of genetically manipulating the neuropeptide GAL on the expression of GALR2 and GALR3 receptors. We found that GAL-tg mice displayed dramatic increases in GAL mRNA and peptide in the frontal cortex, posterior cortex, hippocampus, septal diagonal band complex, amygdala, piriform cortex, and olfactory bulb. Moreover, there was evidence for ectopic neuronal GAL expression in forebrain limbic regions that mediate cognitive and affective behaviors, including the piriform and entorhinal cortex and amygdala. Interestingly, regional qPCR analysis failed to reveal any changes in GALR2 or GALR3 expression in the GAL-tg mice, suggesting that, contrary to GALR1, these receptor genes are not under ligand-mediated regulatory control. The GAL-tg mouse model may provide a useful tool for the investigation of GAL ligand-receptor relationships and their role in normal cognitive and affective functions as well as in the onset of neurological disease. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.