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Neuroscience. 2010 Feb 3;165(3):863-73. doi: 10.1016/j.neuroscience.2009.11.012. Epub 2009 Nov 10.

Group II metabotropic glutamate receptor activation by agonist LY379268 treatment increases the expression of brain derived neurotrophic factor in the mouse brain.

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  • 1Department of Experimental Medicine, Division of Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, Corso Tukory 129, 90134 Palermo, Italy.

Abstract

A number of in vitro and in vivo studies using selective agonists have indicated a neuroprotective role for group-II metabotropic glutamate (mGlu2/3) receptors in various models of neuronal injury. Although an interplay among neurotrophic factors and mGlu2/3 receptors signalling system has been suggested as possible mechanism involved on neuroprotection, at present poor information are available concerning the in vivo regulation by mGlu2/3 receptors activation of specific neurotrophic factors. By using in situ hybridization and western blotting methods the aim of present study was to analyse the potential regulatory role of selective mGluR2/3 agonist LY379268 treatment on brain derived neurotrophic factor (BDNF) expression in the mouse brain. The treatment with LY379268 evidenced a significant upregulation of BDNF mRNA levels in the cerebral cortex and in the hippocampal formation with a peak at 3 h from treatment and its disappearance already at 6 h from treatment. An analysis of dose-effect curve revealed that LY379268 may significantly enhance BDNF mRNA expression already at dose of 0.250 mg/kg b.w. The upregulation of BDNF mRNA expression was followed by a significant increase of BDNF protein levels at 24 h from LY379268 treatment. These effects of LY379268 treatment on BDNF expression were restricted to neuronal cells and were blocked by the new selective mGlu2/3 receptor antagonist LY341495, suggesting a receptor specificity. Taken together these findings suggest that several previous observed neuroprotective and trophic actions of mGluR2/3 agonists treatment may be mediated, at least in the cerebral cortex and hippocampal formation, by upregulation of BDNF expression.

Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

PMID:
19909793
[PubMed - indexed for MEDLINE]
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