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 α-1 (GFRα-1) and c-Ret. In this study, we examined the levels of expression of GFRα-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 GFRα-1 and c-Ret mRNA were determined by in situ hybridization histochemistry. We found that GFRα-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. GFRα-1 mRNA levels in CA3 were gradually up-regulated over the 24-h reperfusion period. In cortex, GFRα-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 GFRα-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 GFRα-1 and c-Ret after ischemia. Since GDNF is neuroprotective, up-regulation of GFRα-1 and c-Ret could enhance the responsiveness to GDNF and reduce neuronal damage. The selective up-regulation of GFRα-1 and c-Ret in different brain areas suggests that there may be regional differences in GDNF-induced neuroprotection in stroke.
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