Holmberg K, Kuteeva E, Brumovsky P, Kahl U, Karlström H, Lucas G A, Rodriguez J, Westerblad H, Hilke S, Theodorsson E, Berge O-G, Lendahl U, Bartfai T, Hökfelt T
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, B3-4, SE-171 77 Stockholm, Sweden.
Neuroscience. 2005;133(1):59-77. doi: 10.1016/j.neuroscience.2005.01.062.
In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes.
在周围神经系统的大部分区域,甘丙肽的表达水平非常低。为了进一步了解甘丙肽的功能作用,构建了一种在血小板衍生生长因子-B作用下过表达甘丙肽的小鼠,并且在几个外周组织和脊髓中观察到了高水平的甘丙肽表达。因此,自主神经节和感觉神经节中的大部分神经元呈甘丙肽阳性,大多数脊髓运动神经元也是如此。在相应的靶组织的神经末梢中也可见强烈的甘丙肽样免疫反应性,这些靶组织包括皮肤、血管、汗腺和唾液腺、运动终板以及脊髓灰质。在转基因的颈上神经节中,大约一半的神经元轮廓表达甘丙肽mRNA,但轴突切断术并未导致其进一步增加,即使个别神经元中的mRNA水平有所升高。在转基因背根神经节中,在大约三分之二的神经元轮廓中检测到了甘丙肽mRNA,包括大型神经元,轴突切断术后,过表达小鼠和野生型小鼠中甘丙肽神经元轮廓的百分比相似。轴突切断术使过表达小鼠的背根神经节神经元总数减少的程度小于野生型小鼠,表明有适度的挽救作用。衰老本身会增加野生型和转基因小鼠颈上神经节中的甘丙肽表达,在转基因小鼠中,投射到颈上神经节的节前胆碱能神经元中甘丙肽表达也会增加。过表达甘丙肽的小鼠表现出血浆外渗减弱、福尔马林试验中的疼痛反应增强以及肌肉生理变化,但在发汗功能方面与野生型小鼠没有差异。这些发现表明,这些小鼠某些组织中过表达的甘丙肽可以释放出来,并通过受体介导的作用影响病理生理过程。