Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse.
Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse.
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DOI：
10.1002/cne.23137
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发表时间：
2012-12-01
影响因子：
2.5
通讯作者：
Elmquist, Joel K.
中科院分区：
文献类型：
--
作者：
Gautron, Laurent;Lee, Charlotte E.;Lee, Syann;Elmquist, Joel K.
黑素皮质素-4受体(MC4R)配体调节伤害性感受，但MC4R信号在伤害性感受中的作用部位尚不清楚。本研究观察了MC4R-GFP报告基因小鼠背根神经节(DRG)中MC4R的表达。由于已知MC4R在结状神经节(NG)的迷走神经传入神经元中表达，我们也系统地比较了表达MC4R的迷走神经和脊髓传入神经元。约45%的DRG神经元(位于胸中水平)存在丰富的绿色荧光蛋白(GFP)免疫反应，其中大部分是小型神经元。免疫组织化学结合原位杂交证实，在背根节内表达MC4R的神经元中确实存在绿色荧光蛋白。在背根神经节中，大量的GFP谱共表达Nav1.8 mRNA(84%)和结合的异凝素B4(72%)，而NF200(16%)或CGRP(13%)的GFP谱相对较少，提示MC4R在C纤维非肽能神经元中优先表达。而在NG中，GFP与Nav1.8mRNA(%)和NF200(29%)频繁共存，但与异凝素B4(16%)仅有中等程度的共存。最后，在NG中很少有GFP谱表达CGRP(5%)或CART(4%)。总之，我们的发现显示了MC4R在不同类别的迷走神经和脊髓初级传入神经元中的不同表达，并强调了黑素皮质素系统在调节伤害性和非伤害性外周感觉方式中的作用。
Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4 (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200 (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.
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