Hou Zhongchi, Miao Yanying, Gao Ling, Pan Hui, Zhu Shigong
Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100083, PR China.
Regul Pept. 2006 May 15;134(2-3):126-31. doi: 10.1016/j.regpep.2006.02.005. Epub 2006 Mar 6.
Ghrelin is a newly discovered brain-gut peptide and an endogenous ligand for growth hormone secretagogues receptor (GHS-R). Ghrelin and GHS-R present extensively in central and peripheral tissues such as stomach, brain and other organs of rodent and human, which suggest it has multiple biological effects. It has been reported that ghrelin has significant role in the regulation of energy homeostasis, food intake and appetite. The organization of central circuitry appears to play an important role in integrating orexigenic effects of ghrelin, but the detail is not fully clear. In this study, we examined the expression of ghrelin, ghrelin mRNA and GHS-R mRNA in cerebrum and brainstem by RT-PCR and immunofluorescence histochemistry, and analyzed the connection among the cerebral cortex, hypothalamus, dorsal vagal complex (DVC). The results showed that the positive staining of ghrelin was found on the pyramidal neuron of layer V in the sensorimotor area of cerebral cortex, cingulate gyrus, as well as in the neuron of lateral hypothalamus (LH), PVN and ARC. The expression of ghrelin mRNA and GHS-R mRNA were also found in the sensorimotor cortex and hypothalamus by method of RT-PCR. The GHS-R mRNA was also found in the DVC of medulla oblongata. Other finding is that the FG/ghrelin dual labeled neurons were found in LH of hypothalamus (not in cortex). The ghrelin-containing neuron in the LH projects its axon to the DVC with the method of retrograde tracing. In conclusion, the ghrelin neurons are located not only in hypothalamus (LH, PVN, ARC), but also in the cortex (sensorimotor area, cingular gyrus), and the fibers of ghrelin neurons in hypothalamus projected directly to the DVC. It suggests that ghrelin plays its role from hypothalamus to brainstem as a neurotransmitter or neuromodulator to regulate function of vagal nuclei in brainstem.
胃饥饿素是一种新发现的脑肠肽，是生长激素促分泌素受体（GHS-R）的内源性配体。胃饥饿素和GHS-R广泛存在于啮齿动物和人类的中枢和外周组织中，如胃、脑和其他器官，这表明它具有多种生物学效应。据报道，胃饥饿素在能量平衡、食物摄入和食欲调节中具有重要作用。中枢神经回路的组织似乎在整合胃饥饿素的促食欲作用中发挥重要作用，但具体细节尚不完全清楚。在本研究中，我们通过逆转录聚合酶链反应（RT-PCR）和免疫荧光组织化学检测了大脑和脑干中胃饥饿素、胃饥饿素mRNA和GHS-R mRNA的表达，并分析了大脑皮层、下丘脑、迷走背核复合体（DVC）之间的联系。结果显示，在大脑皮层感觉运动区、扣带回的V层锥体细胞以及下丘脑外侧区（LH）、室旁核（PVN）和弓状核（ARC）的神经元中发现胃饥饿素阳性染色。通过RT-PCR方法在感觉运动皮层和下丘脑中也发现了胃饥饿素mRNA和GHS-R mRNA的表达。在延髓的DVC中也发现了GHS-R mRNA。另一个发现是，在下丘脑的LH中发现了FG/胃饥饿素双标记神经元（皮层中未发现）。通过逆行追踪方法发现，LH中含胃饥饿素的神经元将其轴突投射到DVC。总之，胃饥饿素神经元不仅位于下丘脑（LH、PVN、ARC），也位于皮层（感觉运动区、扣带回），下丘脑胃饥饿素神经元的纤维直接投射到DVC。这表明胃饥饿素作为神经递质或神经调质从下丘脑到脑干发挥作用，调节脑干迷走神经核的功能。
