Department of Animal and Poultry Sciences, School of Neuroscience, USA.
Department of Animal and Poultry Sciences, School of Neuroscience, USA; Virginia Polytechnic Institute and State University, Blacksburg 24061, VA, USA.
Neuropeptides. 2019 Apr;74:95-102. doi: 10.1016/j.npep.2019.01.003. Epub 2019 Jan 11.
Central administration of corticotropin-releasing factor (CRF), a 41-amino acid peptide, is associated with potent anorexigenic effects in rodents and chickens. However, the mechanism underlying this effect remains unclear. Hence, the objective of the current study was to elucidate the hypothalamic mechanisms that mediate CRF-induced anorexia in 4 day-old Cobb-500 chicks. After intracerebroventricular (ICV) injection of 0.02 nmol of CRF, CRF-injected chicks ate less than vehicle chicks while no effect on water intake was observed at 30 min post-injection. In subsequent experiments, the hypothalamus samples were processed at 60 min post-injection. The CRF-injected chicks had more c-Fos immunoreactive cells in the arcuate nucleus (ARC), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), and paraventricular nucleus (PVN) of the hypothalamus than vehicle-treated chicks. CRF injection was associated with decreased whole hypothalamic mRNA abundance of neuropeptide Y receptor sub-type 1 (NPYR1). In the ARC, CRF-injected chicks expressed more CRF and CRF receptor sub-type 2 (CRFR2) mRNA but less agouti-related peptide (AgRP), NPY, and NPYR1 mRNA than vehicle-injected chicks. CRF-treated chicks expressed greater amounts of CRFR2 and mesotocin mRNA than vehicle chicks in the PVN and VMH, respectively. In the DMN, CRF injection was associated with reduced NPYR1 mRNA. In conclusion, the results provide insights into understanding CRF-induced hypothalamic actions and suggest that the anorexigenic effect of CRF involves increased CRFR2-mediated signaling in the ARC and PVN that overrides the effects of NPY and other orexigenic factors.
促肾上腺皮质释放因子（CRF），一种 41 个氨基酸的肽，在啮齿动物和鸡中与强烈的厌食作用有关。然而，这种作用的机制尚不清楚。因此，本研究的目的是阐明介导 CRF 诱导的 4 日龄 Cobb-500 小鸡厌食的下丘脑机制。在脑室内（ICV）注射 0.02nmol CRF 后，CRF 注射组小鸡的摄食量低于载体组小鸡，而在注射后 30 分钟时，对水的摄入量没有影响。在随后的实验中，在注射后 60 分钟处理下丘脑样本。与载体处理的小鸡相比，CRF 注射的小鸡下丘脑弓状核（ARC）、背内侧核（DMN）、腹内侧下丘脑（VMH）和室旁核（PVN）中的 c-Fos 免疫反应性细胞更多。CRF 注射与下丘脑整体神经肽 Y 受体亚型 1（NPYR1）mRNA 丰度降低有关。在 ARC 中，与载体注射的小鸡相比，CRF 注射的小鸡表达更多的 CRF 和 CRF 受体亚型 2（CRFR2）mRNA，但表达较少的刺鼠相关蛋白（AgRP）、NPY 和 NPYR1 mRNA。与载体组相比，CRF 处理的小鸡在 PVN 和 VMH 中分别表达更多的 CRFR2 和中脑催产素 mRNA。在 DMN 中，CRF 注射与 NPYR1 mRNA 减少有关。总之，这些结果提供了对理解 CRF 诱导的下丘脑作用的深入了解，并表明 CRF 的厌食作用涉及 ARC 和 PVN 中 CRFR2 介导的信号转导增加，从而抵消了 NPY 和其他食欲刺激因子的作用。
