Preproglucagon neurons project widely to autonomic control areas in the mouse brain.
Preproglucagon neurons project widely to autonomic control areas in the mouse brain.
复制标题
DOI：
10.1016/j.neuroscience.2011.02.023
复制
发表时间：
2011-04-28
期刊：
影响因子：
3.3
通讯作者：
Trapp, S.
中科院分区：
文献类型：
--
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
关键词：
胰升糖素样肽1(GLP-1)及其类似物exendin-4通过作用于大脑多个区域的GLP-1受体，抑制食物摄入，降低血糖水平，增加血压和心率。在中枢神经系统中，GLP-1只由前胰高血糖素原(PPG)神经元产生。我们认为PPG神经元通过调节交感神经和迷走神经的外流来调节GLP-1的中枢效应。因此，我们分析了PPG神经元到参与自主神经控制的大脑部位的投射。在PPG启动子控制下表达YFP的转基因小鼠中，我们使用抗GFP抗血清和亲和素-生物素-过氧化物酶来评估YFP免疫反应的神经支配。PPG神经元呈YFP免疫反应阳性，轴突和树突很容易区分。YFP免疫反应阳性胞体主要分布于孤束核尾侧核(NTS)，舌下核腹侧、隐缝核和中间网状核有少量胞体。尾侧NTS含有致密的树突网络，其中一些树突延伸到最后区域。免疫反应阳性轴突广泛分布于NTS、迷走神经背侧核和网状核，舌下核和锥体少见。下丘脑背内侧核、室旁核、中脑导水管周围灰质腹外侧区和丘脑室旁核有较强的神经支配。终板最后区、延髓吻侧腹外侧区、桥脑中央灰质、蓝斑/巴林顿核、弓状核和终板血管器官均有中度神经支配。杏仁核和穹隆下器仅有少量轴突。我们的结果表明，PPG神经元主要支配与自主神经控制有关的脑区。因此，中枢PPG神经元是通过在各种中枢部位的输入来调节交感和副交感神经流出的理想位置。我们的数据还强调，免疫组织化学提高了对表达YFP的神经元的检测。因此，对特定神经元群体进行基因改造以表达荧光蛋白的动物很可能被证明是解剖学研究的理想对象。
Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 inhibit food intake, reduce blood glucose levels and increase blood pressure and heart rate by acting on GLP-1 receptors in many brain regions. Within the central nervous system, GLP-1 is produced only by preproglucagon (PPG) neurons. We suggest that PPG neurons mediate the central effects of GLP-1 by modulating sympathetic and vagal outflow. We therefore analysed the projections of PPG neurons to brain sites involved in autonomic control. In transgenic mice expressing YFP under the control of the PPG promoter, we assessed YFP-immunoreactive innervation using an anti-GFP antiserum and avidin-biotin-peroxidase. PPG neurons were intensely YFP-immunoreactive and axons could be easily discriminated from dendrites. YFP-immunoreactive cell bodies occurred primarily within the caudal nucleus tractus solitarius (NTS) with additional somata ventral to the hypoglossal nucleus, in raphé obscurus and in the intermediate reticular nucleus. The caudal NTS contained a dense network of dendrites, some of which extended into the area postrema. Immunoreactive axons were widespread throughout NTS, dorsal vagal nucleus and reticular nucleus with few in the hypoglossal nucleus and pyramids. The dorsomedial and paraventricular hypothalamic nuclei, ventrolateral periaqueductal grey and thalamic paraventricular nucleus exhibited heavy innervation. The area postrema, rostral ventrolateral medulla, pontine central grey, locus coeruleus/Barrington’s nucleus, arcuate nucleus and the vascular organ of the lamina terminalis were moderately innervated. Only a few axons occurred in the amygdala and subfornical organ. Our results demonstrate that PPG neurons innervate primarily brain regions involved in autonomic control. Thus, central PPG neurons are ideally situated to modulate sympathetic and parasympathetic outflow through input at a variety of central sites. Our data also highlight that immunohistochemistry improves detection of neurons expressing YFP. Hence, animals in which specific populations of neurons have been genetically-modified to express fluorescent proteins are likely to prove ideal for anatomical studies.
登录
查看更多内容
影响因子：
2.8
作者：
Tauchi, Miyuki;Zhang, Rong;Herman, James P.
通讯作者：
Herman, James P.
弧形胰高血糖素样肽1受体调节葡萄糖稳态，但不调节食物摄入量。
影响因子：
7.7
作者：
Sandoval, Darleen A.;Bagnol, Didier;Woods, Stephen C.;D'Alessio, David A.;Seeley, Randy J.
通讯作者：
Seeley, Randy J.
影响因子：
3.3
作者：
Larsen, PJ;TangChristensen, M;Orskov, C
通讯作者：
Orskov, C
影响因子：
4.8
作者：
Hayes, Matthew R.;Skibicka, Karolina P.;Grill, Harvey J.
通讯作者：
Grill, Harvey J.
影响因子：
29
作者：
Reimann F;Habib AM;Tolhurst G;Parker HE;Rogers GJ;Gribble FM
通讯作者：
Gribble FM