Leptin targets in the mouse brain.

Leptin targets in the mouse brain.
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DOI:
10.1002/cne.22025
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发表时间:
2009-06-10
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Elmquist JK
Elmquist JK
中科院分区:
其他
文献类型:
--
作者:
Scott MM;Lachey JL;Sternson SM;Lee CE;Elias CF;Friedman JM;Elmquist JK

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瘦素的中枢作用对于脂肪组织质量、葡萄糖代谢和许多自主神经和神经内分泌系统的动态平衡控制是必不可少的。在大脑中,瘦素通过长型瘦素受体(LepRb)作用于许多不同类型的细胞,从而诱导其作用。准确识别瘦素的细胞靶点是理解其多效性中枢作用机制的基础。我们通过野生型小鼠的原位杂交以及LepRb-IRES-Cre EYFP高水平共表达的新型LepRb-IRES-Cre EYFP报告鼠系的EYFP免疫反应性,系统地研究了LepRb在小鼠脑内的分布。我们发现LepRb mRNA和EYFP在前述的下丘脑和下丘脑外部位有大量的表达,包括下丘脑的背内侧核、乳头体前腹侧核、腹侧被盖区、臂旁核和迷走神经背侧复合体。在岛叶皮质、隔外侧核、视前内侧区、吻侧线状核和Edinger-Westphal核也有表达,以前未见报道。LepRb-IRES-Cre报告线被用来对中脑中一组表达瘦素受体的神经元进行化学表征。酪氨酸羟化酶和Cre报告蛋白在腹侧被盖区和其他中脑多巴胺能神经元中共表达。最后,利用LepRb-IRES-Cre报告线定位中枢神经系统(CNS)LepRb神经元对外周瘦素的感知程度。因此,我们提供了支持使用LepRb-IRES-Cre系来评估表达瘦素受体的神经元的解剖和功能特征的数据。J.Comp.神经。514:518-532,2009。
The central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long-form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin’s cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb-IRES-Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger-Westphal nucleus was also observed and had been previously unreported. The LepRb-IRES-Cre reporter line was used to chemically characterize a population of leptin receptor-expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRb-IRES-Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518–532, 2009.
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