Generation and phenotypic characterization of a galanin overexpressing mouse

被引:52
作者
Holmberg, K
Kuteeva, E
Brumovsky, P
Kahl, U
Karlström, H
Lucas, GA
Rodriguez, J
Westerblad, H
Hilke, S
Theodorsson, E
Berge, OG
Lendahl, U
Bartfai, T
Hökfelt, T
机构
[1] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[3] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
[4] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden
[5] Stockholm Univ, Dept Neurochem & Neurotoxicol, S-10691 Stockholm, Sweden
[6] Linkoping Univ Hosp, Dept Lab Med, S-58185 Linkoping, Sweden
[7] AstraZeneca R&D, Sodertalje, Sweden
[8] Scripps Inst, Harold Dorris Neurol Res Ctr, La Jolla, CA USA
[9] CALTECH, Div Biol, Pasadena, CA 91125 USA
关键词
nerve injury; extravasation; sensory ganglia; sympathetic ganglia; pain;
D O I
10.1016/j.neuroscience.2005.01.062
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.
引用
收藏
页码:59 / 77
页数:19
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