Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4
Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4
复制标题
DOI：
10.1152/ajpregu.00424.2010
复制
发表时间：
2011-10-01
影响因子：
2.8
通讯作者：
Richard, Denis
中科院分区：
文献类型：
--
作者：
Baraboi, Elena-Dana;St-Pierre, David H.;Richard, Denis
[10]杨文，李文. GLP-1受体激动剂毒蜥外泌肽-4外周给药后的脑激活。Am J Physiol Regul Integr Comp Physiol 301：R1011-R1024，2011年。首次发表于2011年7月20日; doi：10.1152/ajpregu.00424.2010.-我们研究的目的是研究不同剂量的毒蜥外泌肽-4（Ex-4）的厌食和大脑刺激作用，并研究迷走神经在Ex-4诱导的大脑激活中的作用。在Ex-4给药（0.155-15.5 μ g/kg）后观察到c-fos mRNA表达的剂量相关性增加。引起厌食而无厌恶作用的Ex-4剂量（0.155，0.775 μ g/kg）诱导下丘脑弓状和室旁（PVH;小细胞）核以及边缘系统和脑干结构中的c-fos表达。引起厌恶的Ex-4剂量（1.55，15.5 μ g/kg）刺激相同区域（以更强烈的方式），并额外激活下丘脑大细胞结构（视上核和PVH大细胞）。Ex-4诱导的脑c-fos模式与再喂养诱导的脑c-fos模式既有相似之处，也有不同之处。延髓下迷走神经切断可明显减弱Ex-4对结状神经节、孤束核内侧部和PVH小细胞分裂区c-fos mRNA表达的刺激作用。用Ex-9-39（330 μ g/kg ip）预处理损害了Ex-4在所有脑区域和结状神经节中诱发的神经元活化。Ex-4对下丘脑-垂体-肾上腺轴活动的影响不受迷走神经切断术的影响。本研究的结果证明并关联了厌恶和非厌恶剂量的Ex-4的厌食和脑刺激作用，并表明通过外周施用Ex-4诱导的特定中心区域的激活至少部分依赖于迷走神经的完整性。
Baraboi E, St-Pierre DH, Shooner J, Timofeeva E, Richard D. Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4. Am J Physiol Regul Integr Comp Physiol 301: R1011-R1024, 2011. First published July 20, 2011; doi:10.1152/ajpregu.00424.2010.-The aim of our study was to investigate the anorectic and brain stimulatory effects of various doses of exendin-4 (Ex-4) and to investigate the role of the vagus nerve in Ex-4-induced brain activation. A dose-related increase in c-fos mRNA expression was observed following Ex-4 administration (0.155-15.5 mu g/kg). Doses of Ex-4 that caused anorexia without aversive effects (0.155, 0.775 mu g/kg) induced c-fos expression in the hypothalamic arcuate and paraventricular (PVH; parvocellular) nuclei as well as in the limbic and brainstem structures. Doses of Ex-4 that caused aversion (1.55, 15.5 mu g/kg) stimulated the same regions (in a more intense way) and additionally activated the magnocellular hypothalamic structures (supraoptic nucleus and PVH magnocellular). The brain c-fos pattern induced by Ex-4 showed both similarities and differences with that induced by refeeding. Subdiaphragmatic vagotomy significantly blunted the stimulation of c-fos mRNA expression induced by Ex-4 in the nodose ganglion, the medial part of nucleus of the solitary tract, and the parvocellular division of the PVH. Pretreatment with Ex-9-39 (330 mu g/kg ip) impaired the neuronal activation evoked by Ex-4 in all brain regions and in the nodose ganglion. Effects of Ex-4 on hypothalamic-pituitary- adrenal axis activity were not altered by vagotomy. Results of this study demonstrate and relate the anorectic and brain stimulatory effects of aversive and nonaversive doses of Ex-4 and indicate that the activation of specific central regions induced by the peripheral administration of Ex-4 is, at least in part, dependent on the integrity of the vagus nerve.