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帕金森病大鼠模型系统中成纤维细胞生长因子-2亚型及成纤维细胞生长因子受体1-4转录本的表达

Expression of the fibroblast growth factor-2 isoforms and the FGF receptor 1-4 transcripts in the rat model system of Parkinson's disease.

作者信息

Claus Peter, Werner Stefan, Timmer Marco, Grothe Claudia

机构信息

Department of Neuroanatomy, Hannover Medical School, OE 4140, Carl-Neuberg-Str.1, 30625 Hannover, Germany.

出版信息

Neurosci Lett. 2004 Apr 29;360(3):117-20. doi: 10.1016/j.neulet.2004.01.046.

Abstract

Basic fibroblast growth factor (FGF)-2 occurs in different isoforms representing different translation products of a single mRNA. We have previously shown that the high molecular weight FGF-2 isoforms (21, 23 kD) stimulated survival- and neurite-promoting activities and protective effects on cultured embryonic dopaminergic (DA) neurons of the substantia nigra (Neuroscience 100 (2000) 73). In this study the expression of FGF-2 isoforms in the striatum and substantia nigra was analyzed by Western blot in adult intact rats and following complete unilateral 6-hydroxydopamine (6-OHDA) lesion. In intact rats, all three FGF-2 isoforms (18, 21, 23 kD) are expressed. Neurotoxin-mediated lesion of nigral DA neurons revealed no change of the FGF-2 isoform expression pattern in the nigrostriatal system. Additionally, the FGF receptors 1, 2 and 3 are expressed in these tissues and displayed no alterations after 6-OHDA injection as demonstrated by RT-PCR. The presence of all three FGF-2 isoforms and the FGFR 1-3, together with the previous demonstrated neurotrophic effects of FGF-2 on dopaminergic neurons, suggest a physiological function of the FGF-2 isoforms in the nigrostriatal system.

摘要

碱性成纤维细胞生长因子(FGF)-2以不同的同工型存在,这些同工型代表单一信使核糖核酸(mRNA)的不同翻译产物。我们先前已表明,高分子量的FGF-2同工型(21、23千道尔顿)可刺激黑质培养的胚胎多巴胺能(DA)神经元的存活和神经突生长活性以及保护作用(《神经科学》100(2000)73)。在本研究中,通过蛋白质免疫印迹法分析了成年完整大鼠以及单侧完全6-羟基多巴胺(6-OHDA)损伤后纹状体和黑质中FGF-2同工型的表达。在完整大鼠中,所有三种FGF-2同工型(18、21、23千道尔顿)均有表达。神经毒素介导的黑质DA神经元损伤显示黑质纹状体系统中FGF-2同工型的表达模式没有变化。此外,FGF受体1、2和3在这些组织中表达,并且如逆转录聚合酶链反应(RT-PCR)所示,6-OHDA注射后没有改变。所有三种FGF-2同工型和FGFR 1-3的存在,以及先前证明的FGF-2对多巴胺能神经元的神经营养作用,提示FGF-2同工型在黑质纹状体系统中具有生理功能。

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