Berthoud Hans-Rudolf, Sutton Gregory M, Townsend R Leigh, Patterson Laurel M, Zheng Huiyuan
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Physiol Behav. 2006 Nov 30;89(4):517-24. doi: 10.1016/j.physbeh.2006.08.018. Epub 2006 Sep 25.
Ingestive behavior is controlled by a complex interplay between signals conveying availability of (1) potentially ingestible food in the environment, (2) digestible food in the alimentary canal, (3) circulating fuels and (4) stored fuels. Each of these four classes of signals interact with specific sensors and neural circuits whose integrated output determines when food intake is initiated and when it is stopped. Because the final common path responsible for oromotor control is contained within complex neural pattern generators within the brainstem and is intimately linked to sensory information from the alimentary canal, at least part of the integration between the four classes of signals is thought to take place at the level of the caudal brainstem. Here we show that CCK, representing a class 2, or direct signal, and MC4-melanocortin receptor activity, representing a second order class 3/4, or indirect signal, converge in the nucleus of the solitary tract where they modulate activity of the mitogen-activated, extracellular-signal regulated kinases 1 and 2 (ERK) pathway to determine the level of satiation. Blockade of this signaling pathway attenuates suppression of deprivation-induced food intake by intraperitoneal CCK and fourth ventricular MTII injection. Additional findings suggest that specific ERK-phosphorylation sites on ion channels and enzymes involved in catecholamine synthesis of NTS neurons may be involved in ERK-mediated satiation and meal termination. Longer-term downstream effects of ERK activation might involve CREB-mediated gene transcription known to produce plasticity changes in neurocircuitry that could determine inter-meal intervals and the size of future meals.
摄食行为受多种信号之间复杂相互作用的控制，这些信号传达了以下方面的可用性：（1）环境中潜在可摄取的食物、（2）消化道中可消化的食物、（3）循环中的燃料以及（4）储存的燃料。这四类信号中的每一类都与特定的传感器和神经回路相互作用，其综合输出决定了何时开始进食以及何时停止进食。由于负责口腔运动控制的最终共同通路包含在脑干内的复杂神经模式发生器中，并且与来自消化道的感觉信息密切相关，因此这四类信号之间的至少部分整合被认为发生在延髓尾部水平。在这里，我们表明，代表第2类或直接信号的胆囊收缩素（CCK）和代表第3/4类或间接信号的促黑素细胞激素4型（MC4）-黑皮质素受体活性，在孤束核中汇聚，在那里它们调节丝裂原活化的细胞外信号调节激酶1和2（ERK）途径的活性，以确定饱腹感水平。阻断该信号通路可减弱腹腔注射CCK和第四脑室注射MTII对剥夺诱导的食物摄入的抑制作用。其他研究结果表明，孤束核神经元中参与儿茶酚胺合成的离子通道和酶上的特定ERK磷酸化位点可能与ERK介导的饱腹感和进餐终止有关。ERK激活的长期下游效应可能涉及CREB介导的基因转录，已知该转录会在神经回路中产生可塑性变化，从而决定餐间间隔和未来餐食的大小。
