Journal
NEUROSCIENCE LETTERS
Volume 379, Issue 3, Pages 185-189Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2004.12.063
Keywords
astrocyte; ifenprodil; neurotrophic factor; nerve growth factor (NGF); brain-derived neurotrophic factor (BDNF); glial cell line-derived neurotrophic factor (GDNF)
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Ifenprodil, a non-competitive NMDA-receptor antagonist, has been shown to exhibit marked cytoprotective activities in animal models for focal ischemia and Parkinson's disease. To test the hypothesis that the cytoprotective effect is due to the release of neurotrophic factors (NTFs), we examined the effects of ifenprodil on the NTF contents in mouse astrocyte cultures. The results revealed that ifenprodil strongly enhanced the production of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in these cultures. The ifenprodil-induced NGF secretion was found to be partially mediated by the activation of protein kinase C (PKC) and p42/p44 mitogen-activated protein (MAP) kinase cascade pathways. These findings suggest that the cytoprotective effects of ifenprodil are probably attributed to enhanced secretion of these NTFs from astrocytes. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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