Immunohistochemical localization of gastrin-releasing peptide receptor in the mouse brain
Immunohistochemical localization of gastrin-releasing peptide receptor in the mouse brain
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DOI：
10.1016/j.brainres.2004.10.068
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发表时间：
2005-01-25
期刊：
影响因子：
2.9
通讯作者：
Wada, K
中科院分区：
文献类型：
--
作者：
Kamichi, S;Wada, E;Wada, K
胃泌素释放肽（GRP）是哺乳动物蛙皮素（BN）样肽，其以高亲和力结合GRP受体（GRP-R）。先前使用小鼠和大鼠的行为研究表明，GRP/GRP-R系统通过调节杏仁核和孤束核（NTS）的局部GABA能网络中的神经递质释放来介导学习和记忆。迄今为止，GRP-R在大脑中的精确分布尚未阐明。我们使用了一种合成肽衍生自小鼠GRP-R产生亲和纯化的抗体GRP-R和免疫组织化学来确定GRP-R在小鼠大脑中的分布。在体外使用瞬时表达GRP-R的COS-7细胞和在体内使用GRP-R缺陷型和野生型小鼠脑切片证实抗GRP-R抗体的特异性。GRP-R免疫阳性反应广泛分布于同侧皮质、海马结构、梨状皮质、杏仁核、下丘脑和脑干。特别是，GRP-R免疫反应观察到外侧（LA），中央和基底外侧杏仁核（BLA）和NTS，这是记忆性能的重要区域。免疫组化双标记结果表明，杏仁核内GABA能神经元中存在GRP-R亚群。因此，在边缘区的GABA能神经元中观察到GRP-R免疫反应性。这些解剖学结果为GRP/GRP-R系统通过调节局部GABA能网络中的神经递质释放来介导记忆表现的观点提供了支持。(C)2004 Elsevier B. V.保留所有权利。
Gastrin-releasing peptide (GRP) is a mammalian bombesin (BN)-like peptide that binds with high affinity to the GRP receptor (GRP-R). Previous behavioral studies using mice and rats showed that the GRP/GRP-R system mediates learning and memory by modulating neurotransmitter release in the local GABAergic network of the amygdala and the nucleus tractus solitarius (NTS). To date, the precise distribution of GRP-R in the brain has not been elucidated. We used a synthetic peptide derived from mouse GRP-R to generate affinity-purified antibodies to GRP-R and used immunohistochemistry to determine the distribution of GRP-R in the mouse brain. The specificity of anti-GRP-R antibody was confirmed in vitro using COS-7 cells transiently expressing GRP-R and in vivo using GRP-R-deficient and wild-type mouse brain sections. GRP-R immunoreactivity was widely distributed in the isocortex, hippocampal formation, piriform cortex, amygdala, hypothalamus, and brain stem. In particular, GRP-R immunoreactivity was observed in the lateral (LA), central, and basolateral amygdaloid (BLA) nuclei and NTS, which are important regions for memory performance. Double-labeling immunohistochemistry demonstrated that subpopulations of GRP-R are present in GABAergic neurons in the amygdala. Consequently, GRP-R immunoreactivity was observed in the GABAergic neurons of the limbic region. These anatomical results provide support for the idea that the GRP/GRP-R system mediates memory performance by modulating neurotransmitter release in the local GABAergic network. (C) 2004 Elsevier B.V. All rights reserved.