GDNF family receptors are differentially regulated by mild or severe reversible focal ischemia in the rat brain

GDNF family receptors are differentially regulated by mild or severe reversible focal ischemia in the rat brain

Field: Disorders of the nervous system

Authors: Arvidsson, Andreas

Address of presenting
author: Andreas Arvidsson
Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden

E-mail: andreas.arvidsson@neurol.lu.se

Phone: 046-2220551

Fax: 046-2220560

Text of abstract: The GDNF family of neurotrophic factors consists of Glial cell-line derived neurotrophic factor (GDNF), Neurturin (NTN), Persephin (PSP) and Artemin (ART). In order to clarify the role of these proteins in the patophysiologic processes after focal cerebral ischemia, we studied the post-ischemic expression patterns of GDNF family ligand and receptor mRNAs. Rats were subjected to sham surgery or middle cerebral artery occlusion (MCAO), a model of focal cerebral ischemia, for 30 min or 2 h. 2h, 6h, 24h or 1 week post ischemia, rats were killed and in situ hybridization was performed using probes for GDNF, NTN, PSP and receptor proteins GFRa1, GFRa2 and c-Ret. Except for an early increase of GDNF mRNA in the dentate gyrus, no changes of ligand expression occurred. However, mRNA levels for both GFRa1, which is the GDNF co-receptor, and c-Ret, the signal transducing receptor, but not GFRa2, the NTN co-receptor, were strongly increased in peri-infarct cortical areas after 2h of MCAO, which gives rise to a corticostriatal lesion, and in striatum as well as cortex after 30 min of MCAO, which causes striatal damage only. Peak values were at 6h or 24h. Changes also occurred in thalamus and hippocampus. These data indicate that GDNF family signalling is regulated mainly through altered receptor levels, and suggest a specific role for GDNF in the post-ischemic brain. The fact that receptors for GDNF are upregulated in cortex and striatum after focal cerebral ischemia is also of interest for possible future therapeutic approaches using exogenous supply of GDNF.

Keywords: GDNF, gene expression, mRNA, in situ hybridization, focal cerebral ischemia

	GDNF family receptors are differentially regulated by mild or severe reversible focal ischemia in the rat brain
Field:	Disorders of the nervous system
Authors:	Arvidsson, Andreas
Address of presenting author:	Andreas Arvidsson Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden
E-mail:	andreas.arvidsson@neurol.lu.se
Phone:	046-2220551
Fax:	046-2220560
Text of abstract:	The GDNF family of neurotrophic factors consists of Glial cell-line derived neurotrophic factor (GDNF), Neurturin (NTN), Persephin (PSP) and Artemin (ART). In order to clarify the role of these proteins in the patophysiologic processes after focal cerebral ischemia, we studied the post-ischemic expression patterns of GDNF family ligand and receptor mRNAs. Rats were subjected to sham surgery or middle cerebral artery occlusion (MCAO), a model of focal cerebral ischemia, for 30 min or 2 h. 2h, 6h, 24h or 1 week post ischemia, rats were killed and in situ hybridization was performed using probes for GDNF, NTN, PSP and receptor proteins GFRa1, GFRa2 and c-Ret. Except for an early increase of GDNF mRNA in the dentate gyrus, no changes of ligand expression occurred. However, mRNA levels for both GFRa1, which is the GDNF co-receptor, and c-Ret, the signal transducing receptor, but not GFRa2, the NTN co-receptor, were strongly increased in peri-infarct cortical areas after 2h of MCAO, which gives rise to a corticostriatal lesion, and in striatum as well as cortex after 30 min of MCAO, which causes striatal damage only. Peak values were at 6h or 24h. Changes also occurred in thalamus and hippocampus. These data indicate that GDNF family signalling is regulated mainly through altered receptor levels, and suggest a specific role for GDNF in the post-ischemic brain. The fact that receptors for GDNF are upregulated in cortex and striatum after focal cerebral ischemia is also of interest for possible future therapeutic approaches using exogenous supply of GDNF.

Keywords:	GDNF, gene expression, mRNA, in situ hybridization, focal cerebral ischemia

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Created 2000-03-14

Department of Physiological Sciences, Lund University

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