Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus.

Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus.
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DOI:
10.1002/cne.23273
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发表时间:
2013-07-01
影响因子:
2.5
通讯作者:
Maratos-Flier, Eleftheria
Maratos-Flier, Eleftheria
中科院分区:
医学3区
文献类型:
--
作者:
Chee, Melissa J. S.;Pissios, Pavlos;Maratos-Flier, Eleftheria

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黑色素浓集激素(MCH)是一种下丘脑神经肽,通过MCH受体1(MCHR 1)在小鼠中发挥作用。它促进正能量平衡,因此缺乏MCH或MCHR 1的小鼠是瘦的,多动的,并且抵抗饮食诱导的肥胖。确定MCH的细胞靶点是理解MCH作用机制的重要一步。我们产生了表达由MCHR 1启动子驱动的cre重组酶的Mchr 1-cre小鼠,并将其与tdTomato报告小鼠杂交。由此产生的Mchr 1-cre/tdTomato后代在MCHR 1神经元中表达容易检测到的tdTomato荧光,这些神经元在整个嗅觉系统、纹状体和下丘脑中被发现。为了化学鉴定在能量平衡中起作用的MCH靶向细胞群,通过用tdTomato荧光共标记选择的下丘脑神经肽来表征MCHR 1下丘脑神经元。TdTomato荧光与室旁核中的强啡肽、催产素、加压素、脑啡肽、促甲状腺激素释放激素和促肾上腺皮质激素释放因子免疫反应细胞共定位。在外侧下丘脑,神经降压素,但没有食欲素也MCH神经元表达tdTomato。在弓状核,神经肽Y和proopiomelanocortin细胞表达tdTomato。我们进一步证明了这些弓状神经元中的一些也是瘦素作用的靶点。有趣的是,MCHR 1在绝大多数瘦素敏感的proopiomelanocortin神经元中表达,突出了它们对MCH的食欲作用的重要性。总之,本研究支持使用Mchr 1-cre小鼠概述MCHR 1神经元的神经解剖分布和神经化学表型。
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance thus mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet-induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1-cre mouse that expressed cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1-cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH-targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin-releasing hormone, and corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin but neither orexin nor MCH neurons expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin-sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1-cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons.
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