Melanocortin receptor 4 is induced in nerve‐injured motor and sensory neurons of mouse
Melanocortin receptor 4 is induced in nerve‐injured motor and sensory neurons of mouse
复制标题
DOI：
10.1111/j.1471-4159.2006.04432.x
复制
发表时间：
2007-05
影响因子：
4.7
通讯作者：
K. Tanabe;Kazushige Gamo;S. Aoki;K. Wada;H. Kiyama
中科院分区：
文献类型：
--
作者：
K. Tanabe;Kazushige Gamo;S. Aoki;K. Wada;H. Kiyama
我们以前确定黑皮质素受体4（MC 4 R）在寻找与舌下神经再生相关的基因。由于黑皮质素促进轴突损伤后的神经再生，我们研究了MC 4 R是否作为周围神经再生的关键受体。原位杂交显示，MC 4 R mRNA诱导小鼠舌下神经运动神经元轴突损伤后，而MC 1 R，MC 2 R，MC 3R和MC 5 R的mRNA不表达之前或之后的神经损伤。该结果通过RT-PCR得到证实。MC 4 R mRNA表达水平从切断后第3天开始显著升高，第5天达到高峰，第14天降至对照水平。在轴突切断的小鼠背根神经节（DRG）中观察到类似的MC 4 R诱导。坐骨神经损伤后，仅在L4 - 6 DRG中的MCR家族中诱导MC 4 R mRNA表达。我们进一步研究了α-黑皮质素刺激激素（α-MSH）是否通过MC 4 R促进神经突延伸。在小鼠DRG神经元培养中，α-MSH在10−8 mol/L的浓度下显著促进神经突生长。添加选择性MC 4 R阻断剂JKC-363完全抑制了这种神经突延长作用。因此，可以得出结论，α-MSH可以通过MC 4 R刺激DRG神经元中的神经突延伸。目前的结果表明，MC 4 R的诱导是至关重要的运动和感觉神经元轴突损伤后再生。
We previously identified melanocortin receptor 4 (MC4R) in a search for genes associated with hypoglossal nerve regeneration. As melanocortins promote nerve regeneration after axonal injury, we investigated whether MC4R functions as a key receptor for peripheral nerve regeneration. In situ hybridization revealed that MC4R mRNA is induced in mouse hypoglossal motor neurons after axonal injury, whereas mRNAs for MC1R, MC2R, MC3R, and MC5R are not expressed either before or after nerve injury. This result was confirmed by RT‐PCR. The level of MC4R mRNA expression increased significantly from day 3 after axotomy, reached a peak on day 5, and decreased to the control level on day 14. Similar induction of MC4R was observed in axotomized mouse dorsal root ganglia (DRGs). MC4R mRNA expression was induced exclusively among the MCR family in the L4‐6 DRG after sciatic nerve injury. We further examined whether alpha‐melanocortin stimulating hormone (alpha‐MSH) promotes neurite elongation via MC4R. In mouse DRG neuron culture, alpha‐MSH significantly promoted neurite outgrowth at a concentration of 10−8 mol/L. This neurite‐elongation effect was entirely inhibited by the addition of a selective MC4R blocker, JKC‐363. Therefore, it is concluded that alpha‐MSH could stimulate neurite elongation via MC4R in DRG neurons. The present results suggest that induction of MC4R is crucial for motor and sensory neurons to regenerate after axonal injury.