The messenger RNAs for both glial cell line-derived neurotrophic factor receptors, c-ret and GDNFRα, are induced in the rat brain in response to kainate-induced excitation

Glial cell line-derived neurotrophic factor (GDNF) has two receptors, receptor-tyrosine kinase c-rer and glycosylphosphatidylinositol-linked cell surface receptor GDNFR alpha. Kainate-induced seizures, a widely studied model of neuronal plasticity and human epilepsy, have been shown to increase gene expression of several trophic Factors, including GDNF, in the rat hippocampus. Here we show that systemic kainate-induced excitation leads to a transient increase of both c-ret and GDNFR alpha messenger RNAs in the rat brain. Northern analysis demonstrated that, in the hippocampus, the maximal 2.5-fold increase of c-ret and four-fold increase of GDNFR alpha messenger RNAs was observed after 12 h of kainate injection, in contrast to GDNF messenger RNA, which reaches its maximum in 4-6 h. The blocking of de novo protein synthesis by cycloheximide inhibited the induction of GDNF receptors by kainate, whereas blocking of the iv-methyl-D-aspartate-type glutamate receptors by the antagonist dizocilpine maleate did not significantly alter the response. Thus, GDNF receptor messenger RNA increase by kainate depends on protein synthesis, but is not mediated by the N-methyl-D-aspartate receptor. GDNFR alpha and c-ret show distinct, but partially overlapping, patterns of expression in the brain after kainate treatment. GDNFR alpha messenger RNA was prominently induced in the dentate gyrus of the rat hippocampus, less in the habenular and reticular thalamic nuclei and cerebral cortex as revealed by in situ hybridization. C-ret transcripts were induced in the hilus of the hippocampus, several thalamic and amygdala nuclei and in superficial layers of the piriform cortex. These data suggest that GDNF and its receptors may play a local role in neuronal plasticity and in neuronal protection following epileptic insults. (C) 1997 IBRO. Published by Elsevier Science Ltd.