Glial cell line derived neurotrophic factor (GDNF) promotes neuronal survival in vitro and in vivo. Previous studies have shown that intracerebral administration of GDNF reduces infarction in the cortex (Wang et al. 1997) induced by middle cerebral artery occlusion (MCA-O) and subsequent reperfusion. The participation of endogenous GDNF during stroke has been suggested from northern blot analysis showing that GDNF transcripts are induced one hour after reperfusion (Abe et al. 1997). GDNF exerts its biological activity by binding to its receptor GFR a-1 and transferring its signal through c-ret. Thus, we evaluate possible changes in GFR a-1 and c-ret expression in a rat model of stroke produced by MCA-O. Using in situ hybridization, we detected upregulation of GFR a-1 expression in cortex, dentate gyrus and hippocampus. The peak of expression was 6-12 hrs after reperfusion. Interestingly, c-ret expression was also upregulated in cortex and hippocampus but 12-24 hrs after reperfusion. In normal adult rat brain, GFR a-1 expression in hippocampus is associated with parvalbumin immunoreactive neurons. We are currently investigating the phenotypic population of the cells that undergo preferential upregulation of GFR a-1 and c-ret after MCA-O. This information will permit better understanding the cellular components that participate in the effects of GDNF during stroke.
| Sarabi, A; Hoffer, B J; Olson, L et al. (2003) Glial cell line neurotrophic factor-family receptor alpha-1 is present in central neurons with distinct phenotypes. Neuroscience 116:261-73 |
| Sarabi, A; Chang, C F; Wang, Y et al. (2001) Time course study of GFRalpha-1 expression in an animal model of stroke. Exp Neurol 170:283-9 |
