Characterization Of Gdnf Alpha 1 (gfr Alpha 1) Receptor

Gdnf Alpha 1 (gfr Alpha 1) 受体的表征

• 批准号: 6535531
• 负责人: BARRY J. HOFFER
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6535531
• 关键词: cerebral cortex; growth factor receptors; hippocampus; laboratory rat; neuroprotectants; neurotrophic factors; receptor expression; stroke

Previous studies have shown that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) reduces ischemia-mediated cerebral infarction. The biological effects of GDNF are mediated by GDNF-family receptor alpha-1 (GFRalpha-1) and c-Ret. In this study, we examined the levels of expression of GFRalpha-1 and c-Ret in a rat model of stroke. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. The right middle cerebral artery was ligated at its distal branch for 90 min. Animals were sacrificed at 0, 6, 12, and 24 h after reperfusion and levels of expression of GFRalpha-1 and c-Ret mRNA were determined by in situ hybridization histochemistry. We found that GFRalpha-1 mRNA was up-regulated in CA3, dentate gyrus (DG), cortex, and striatum. The peak of up-regulation in DG was 6 h after reperfusion. GFRalpha-1 mRNA levels in CA3 were gradually up-regulated over the 24-h reperfusion period. In cortex, GFRalpha-1 mRNA was up-regulated at all time points; however, the peak of up-regulation was observed at 0 and 24 h after reperfusion. In striatum, an initial up-regulation of GFRalpha-1 was found at 0 h after ischemia. In striatum, up-regulation of c-Ret mRNA was detected as early as 0 h after reperfusion. A gradual increase was found at 6, 12, and 24 h after reperfusion. In conclusion, our results indicate that there are both regional and temporal differences in up-regulation of GFRalpha-1 and c-Ret after ischemia. Since GDNF is neuroprotective, up-regulation of GFRalpha-1 and c-Ret could enhance the responsiveness to GDNF and reduce neuronal damage. The selective up-regulation of GFRalpha-1 and c-Ret in different brain areas suggests that there may be regional differences in GDNF-induced neuroprotection in stroke. Copyright 2001 Academic Press.

以往的研究表明，脑内应用胶质细胞源性神经营养因子(GDNF)可减少脑缺血所致的脑梗塞。GDNF的生物学效应由GDNF家族受体α-1(GFRα-1)介导 和c-Ret。在这项研究中，我们检测了GFRpha-1和c-Ret在中风大鼠模型中的表达水平。成年SD大鼠用水合氯醛麻醉。结扎右侧大脑中动脉远端支90min。分别于再灌注0、6、12、24 h处死动物，用原位杂交组织化学方法检测GFRAlpha-1和c-Ret的表达水平。我们发现GFRpha-1mRNA在CA3、齿状回、皮质和纹状体表达上调。DG表达上调高峰在再灌流后6h。再灌流24小时后，CA3区GFRAlpha-1mRNA表达逐渐上调。在大脑皮层，GFRpha-1mRNA在各时间点均有上调，但在再灌流后0和24 h达高峰。在纹状体，GFRAlpha-1在缺血后0h开始表达上调。纹状体区c-Ret基因表达上调早在再灌流后0h。再灌流后6、12、24 h逐渐增加。综上所述，我们的结果表明，缺血后GFRAlpha-1和c-Ret的上调存在区域和时间上的差异。由于GDNF具有神经保护作用，上调GFRpha-1和c-Ret可以增强对GDNF的反应性，减少神经元损伤。GFRAlpha-1和c-Ret在不同脑区的选择性上调提示，GDNF在卒中诱导的神经保护作用可能存在区域性差异。学术出版社版权所有2001年。