Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164
Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164.
J Neurosci. 2014 Sep 17;34(38):12636-45. doi: 10.1523/JNEUROSCI.1121-14.2014.
Injection of the melanocortin-3/4 receptor agonist melanotan-II (MTII) into the nucleus of the solitary tract (NTS) produces rapid and sustained reduction of food intake. Melanocortin-4 receptors (MC4Rs) are expressed by vagal afferent endings in the NTS, but it is not known whether these endings participate in MTII-induced reduction of food intake. In experiments described here, we evaluated the contribution of central vagal afferent endings in MTII-induced reduction of food intake. Examination of rat hindbrain sections revealed that neuronal processes expressing immunoreactivity for the endogenous MC4R agonist α-melanoctyte-stimulating hormone course parallel and wrap around anterogradely labeled vagal afferent endings in the NTS and thus are aptly positioned to activate vagal afferent MC4Rs. Furthermore, MTII and endogenous MC4R agonists increased protein kinase A (PKA)-catalyzed phosphorylation of synapsin I in vagal afferent endings, an effect known to increase synaptic strength by enhancing neurotransmitter release in other neural systems. Hindbrain injection of a PKA inhibitor, KT5720, significantly attenuated MTII-induced reduction of food intake and the increase in synapsin I phosphorylation. Finally, unilateral nodose ganglion removal, resulting in degeneration of vagal afferent endings in the ipsilateral NTS, abolished MTII-induced synapsin I phosphorylation ipsilateral to nodose ganglion removal. Moreover, reduction of food intake following MTII injection into the NTS ipsilateral to nodose ganglion removal was significantly attenuated, whereas the response to MTII was not diminished when injected into the contralateral NTS. Altogether, our results suggest that reduction of food intake following hindbrain MC4R activation is mediated by central vagal afferent endings.
注射黑色素皮质素-3/4 受体激动剂黑素细胞刺激素 II（MTII）到孤束核（NTS）中会迅速而持续地减少食物摄入。MC4 受体（MC4Rs）在 NTS 中的迷走传入末梢表达，但尚不清楚这些末梢是否参与 MTII 诱导的食物摄入减少。在本文描述的实验中，我们评估了中枢迷走传入末梢在 MTII 诱导的食物摄入减少中的作用。对大鼠后脑切片的检查显示，表达内源性 MC4R 激动剂α-黑素细胞刺激素免疫反应性的神经元过程与 NTS 中顺行标记的迷走传入末梢平行并环绕，因此非常适合激活迷走传入 MC4Rs。此外，MTII 和内源性 MC4R 激动剂增加了迷走传入末梢中蛋白激酶 A（PKA）催化的突触素 I 磷酸化，这种效应已知通过增强其他神经系统中的神经递质释放来增强突触强度。后脑注射 PKA 抑制剂 KT5720 显著减弱了 MTII 诱导的食物摄入减少和突触素 I 磷酸化的增加。最后，单侧结状神经节切除导致同侧 NTS 中迷走传入末梢变性，消除了 MTII 诱导的突触素 I 磷酸化。此外，结状神经节切除同侧 NTS 注射 MTII 后，食物摄入减少明显减弱，而当注射到对侧 NTS 时，MTII 的反应并未减弱。总之，我们的结果表明，后脑 MC4R 激活后食物摄入减少是由中枢迷走传入末梢介导的。
