Characterization of neuropeptide YY2 and Y5 receptor expression in the mouse hypothalamus
Characterization of neuropeptide YY2 and Y5 receptor expression in the mouse hypothalamus
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DOI：
10.1002/cne.11047
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发表时间：
2004-03-08
影响因子：
2.5
通讯作者：
Hökfelt, T
中科院分区：
文献类型：
--
作者：
Fetissov, SO;Byrne, LC;Hökfelt, T
神经肽 Y (NPY) 神经元大量支配下丘脑，其中 NPY 参与多种稳态功能的调节。在目前的工作中，我们通过使用β-半乳糖苷酶（β-gal）的免疫组织化学检测来研究小鼠下丘脑中的NPY Y2和Y5受体（R）基因表达，β-半乳糖苷酶是Y2R敲除（KO）和Y5R-KO小鼠中Y2R和Y5R的基因报告分子，分别。通过这种方法，通常表达 Y2R 或 Y5R 的细胞对 β-gal 呈免疫阳性。在 Y2R-KO 小鼠的下丘脑中，在内侧视前核以及外侧前核、室周核、背内侧核、结节核、穹窿周核和弓状核的许多神经元中发现了 β-gal 免疫反应性 (-ir)。 A13下丘脑背侧组中的大多数多巴胺能神经元呈P-gal阳性，而其他下丘脑多巴胺能神经元很少呈β-gal-ir阳性。在弓状核中，大多数β-gal阳性神经元表达NPY，但也发现与β-内啡肽的共定位；在结节和穹窿周核中，许多β-gal阳性神经元含有一氧化氮合酶。 beta-Gal-ir 也在 Y2R-KO 小鼠的其他前脑区域中发现，包括杏仁核、丘脑核、海马 CA3 区和皮质。在Y5R-KO小鼠的下丘脑中，β-gal阳性神经元主要存在于弓状核中并含有β-内啡肽。目前的数据表明，Y2R 和 Y5R 在不同的下丘脑神经元组中表达。视前核中高水平的 Y2R 表达表明 Y2R 参与生殖行为的调节，而弓状核、背内侧核和穹窿周核中的 Y2R 表达可能与摄食和体重控制有关。 A13 多巴胺能神经元表达 Y2R 的发现表明，一种可能参与摄食中枢控制的新机制，其中 NPY 可以调节多巴胺分泌。 Y5R 表达的分布支持了早期证据，表明该受体通过 NPY 对表达原阿黑皮素的神经元的作用来参与控制摄食和体重。 (C) 2004 Wiley-Liss, Inc.
Neuropeptide Y (NPY) neurons abundantly innervate the hypothalamus, where NPY is involved in the regulation of a broad range of homeostatic functions. In the present work we studied NPY Y2 and Y5 receptor (R) gene expression in the mouse hypothalamus by using immunohistochemical detection of beta-galactosidase (beta-gal), a gene reporter molecule for Y2R and Y5R in Y2R-knockout (KO) and Y5R-KO mice, respectively. With this approach, cells normally expressing Y2R or Y5R are immunopositive for beta-gal. In the hypothalamus of the Y2R-KO mouse, beta-gal immunoreactivity (-ir) was found in numerous neurons of the medial preoptic nucleus as well as in the lateral anterior, periventricular, dorsomedial, tuberal, perifornical, and arcuate nuclei. Most of the dopaminergic neurons in the A13 dorsal hypothalamic group were P-gal positive, whereas other hypothalamic dopaminergic neurons rarely displayed beta-gal-ir. In the arcuate nucleus, most of the beta-gal-positive neurons expressed NPY, but colocalizations with beta-endorphin were also found; in the tuberal and perifornical nuclei, many beta-gal-positive neurons contained nitric oxide synthase. beta-Gal-ir was also found in other forebrain regions of the Y2R-KO mouse, including the amygdala, thalamic nuclei, hippocampal CA3 area, and cortex. In the hypothalamus of the Y5R-KO mouse, beta-gal-positive neurons were found mainly in the arcuate nucleus and contained beta-endorphin. The present data show that Y2R and Y5R are expressed in distinct groups of hypothalamic neurons. High levels of Y2R expression in the preoptic nuclei suggest an involvement of Y2R in the regulation of reproductive behavior, whereas Y2R expression in the arcuate, dorsomedial, and perifornical nuclei may be relevant to feeding and body weight control. The finding that A13 dopaminergic neurons express Y2R suggests a new mechanism putatively involved in the central control of feeding, in which NPY can modulate dopamine secretion. The distribution of Y5R expression supports earlier evidence for involvement of this receptor in control of feeding and body weight via NPY's action on proopiomelanocortin-expressing neurons. (C) 2004 Wiley-Liss, Inc.