title: Time course study of GFRalpha-1 expression in an animal model of stroke.
abstract: 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.
authors.affiliation: National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sarabi
authors.forename: C F
authors.initials: CF
authors.lastname: Chang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: B J
authors.initials: BJ
authors.lastname: Hoffer
authors.forename: M
authors.initials: M
authors.lastname: Morales
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D020768:Middle Cerebral Artery; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015424:Reperfusion; D020521:Stroke / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; C494989:Gfra1 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat