Distribution of angiotensin type 1a receptor-containing cells in the brains of bacterial artificial chromosome transgenic mice.
Distribution of angiotensin type 1a receptor-containing cells in the brains of bacterial artificial chromosome transgenic mice.
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DOI：
10.1016/j.neuroscience.2012.08.039
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发表时间：
2012-12-13
期刊：
影响因子：
3.3
通讯作者：
Milner, T. A.
中科院分区：
文献类型：
--
作者：
Gonzalez, A. D.;Wang, G.;Waters, E. M.;Gonzales, K. L.;Speth, R. C.;Van Kempen, T. A.;Marques-Lopes, J.;Young, C. N.;Butler, S. D.;Davisson, R. L.;Iadecola, C.;Pickel, V. M.;Pierce, J. P.;Milner, T. A.
关键词：
在中枢神经系统中，血管紧张素II（AngII）与血管紧张素1型受体（AT 1 R）结合，影响自主神经和内分泌功能以及学习和记忆。然而，了解含有AT 1 Rs的细胞的功能受到限制，有限的可用性特定的抗血清，难以区分AT 1受体免疫反应性细胞在许多脑区，并识别AT 1 R-含有神经元的生理和分子研究。在这里，我们证明了一个Agtr 1a细菌人工染色体（BAC）转基因小鼠品系，表达A型AT 1 Rs（AT 1aRs）的增强型绿色荧光蛋白（EGFP）确定克服了这些缺点。在整个脑中，AT 1aR-EGFP在细胞的细胞核和细胞质中被检测到，其中大部分是神经元。EGFP通常延伸到树突状突起中，并且可以天然地或用EGFP的免疫标记来鉴定。AT 1aR-EGFP细胞在脑中的分布与AngII结合和AT 1aR蛋白和mRNA的报道密切相关。特别地，AT 1aR-EGFP细胞位于自主区域（例如，下丘脑室旁核、杏仁核中央核、臂旁核、孤束核和延髓头端腹外侧核）和涉及电解质和液体平衡的区域（即，穹窿下器官）和学习和记忆（即，大脑皮层和海马体）。此外，在选定的脑区的双标记电子显微镜研究表明，细胞含有AT 1aR-EGFP与AT 1 R免疫反应共定位。在分离的EGFP细胞中AngII诱导的自由基产生的评估证明了研究离体AT 1aR信号转导的可行性。这些发现支持Agtr 1a BAC转基因报告小鼠用于未来研究的效用，了解AT 1受体细胞在脑功能中的作用。
In the central nervous system, angiotensin II (AngII) binds to angiotensin type 1 receptors (AT1R) to affect autonomic and endocrine functions as well as learning and memory. However, understanding the function of cells containing AT1Rs has been restricted by limited availability of specific antisera, difficulties discriminating AT1 receptor-immunoreactive cells in many brain regions and, the identification of AT1R-containing neurons for physiological and molecular studies. Here, we demonstrate that an Agtr1a bacterial artificial chromosome (BAC) transgenic mouse line that expresses type A AT1Rs (AT1aRs) identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, AT1aR-EGFP was detected in the nuclei and cytoplasm of cells, most of which were neurons. EGFP often extended into dendritic processes and could be identified either natively or with immunolabeling of EGFP. The distribution of AT1aR-EGFP cells in brain closely corresponded to that reported for AngII binding and AT1aR protein and mRNA. In particular, AT1aR-EGFP cells were in autonomic regions (e.g., hypothalamic paraventricular nucleus, central nucleus of the amygdala, parabrachial nucleus, nuclei of the solitary tract and rostral ventrolateral medulla) and in regions involved in electrolyte and fluid balance (i.e., subfornical organ) and learning and memory (i.e., cerebral cortex and hippocampus). Additionally, dual label electron microscopic studies in select brain areas demonstrate that cells containing AT1aR-EGFP colocalize with AT1R-immunoreactivity. Assessment of AngII-induced free radical production in isolated EGFP cells demonstrated feasibility of studies investigating AT1aR signaling ex vivo. These findings support the utility of Agtr1a BAC transgenic reporter mice for future studies understanding the role of AT1 receptor containing cells in brain function.
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影响因子：
3.3
作者：
Dumont, EC;Rafrafi, S;Drolet, G
通讯作者：
Drolet, G
影响因子：
3.3
作者：
Glass, MJ;Huang, J;Pickel, VM
通讯作者：
Pickel, VM
DOI：
10.1002/cne.22272
发表时间：
2010-04-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Drouyer E;LeSauter J;Hernandez AL;Silver R
通讯作者：
Silver R
影响因子：
2.5
作者：
Bulloch, Karen;Miller, Melinda M.;McEwen, Bruce S.
通讯作者：
McEwen, Bruce S.
影响因子：
2.9
作者：
Hayward, Linda F.
通讯作者：
Hayward, Linda F.