PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.
PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.
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DOI：
10.1152/ajpregu.00333.2015
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
S. Trapp;Simon C. Cork
中科院分区：
文献类型：
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作者：
S. Trapp;Simon C. Cork
在大脑中，胰高血糖素样肽 1 (GLP-1) 影响中枢自主神经元，包括控制心血管系统、产热和能量平衡的神经元。此外，GLP-1 影响中脑边缘奖励系统，以调节可口食物的奖励特性。 GLP-1 在肠道中由后脑前胰高血糖素原 (PPG) 神经元产生，主要位于孤束核 (NTS) 和髓质中间网状核中。表达胰高血糖素启动子驱动的黄色荧光蛋白的转基因小鼠表明，PPG 神经元不仅投射到中央自主控制区和中脑边缘奖赏中心，而且还强烈支配脊髓自主神经元。因此，这些脑干 PPG 神经元可以通过其脊髓输入直接调节交感神经流出到交感神经节前神经元。体外 PPG 神经元的电记录表明，它们接收来自通过孤束进入的迷走神经传入的突触输入。迷走神经传入将饱腹感从餐后胃扩张或外周 GLP-1 受体激活等信号传递到大脑。 CCK 和瘦素（短期和长期饱腹感肽）分别增加 PPG 神经元的电活动，而胃饥饿素（一种促食欲肽）则没有效果。这些发现表明饱足感是 PPG 神经元激活的主要驱动力。他们还表明，PPG 神经元处于对能量和进食状态的即时和长期指标做出反应的主要位置，从而能够调节能量平衡和一般自主神经稳态。这篇综述讨论了 PPG 神经元（而不是肠道来源的 GLP-1）是否为中枢神经系统 GLP-1 受体激活引起的效应提供生理基质的问题。
Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.