Document Detail

Glutamate stimulates neurotrophin expression in cultured Müller cells.
MedLine Citation:
PMID:  12654519     Owner:  NLM     Status:  MEDLINE    
The uptake of excess extracellular glutamate and the secretion of neurotrophins by glial cells have been suggested to protect CNS neurons from glutamate-induced toxicity. In the retina, perturbation of glutamate transport and decreased retrograde transport of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) may contribute to ganglion cell death in experimental glaucoma. Although many studies show a clear relationship between glutamate and neurotrophic factors, such relationship has not been thoroughly investigated in the retinal environment. In the following study, we determined the effects of glutamate on early passaged rat Müller cells, specifically their expression of neurotrophic factors including BDNF, nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and glial-cell line derived neurotrophic factor (GDNF); and of glutamate receptors and transporters using immunoblots or enzyme-linked immunosorbent assays. Binding of BDNF to its cognate receptor TrkB was also determined using co-immunoprecipitation studies. Cultured Müller cells grown in the presence of glutamate were also assayed for survival using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Our study showed that while glutamate treatment did not promote cell death, it upregulated secretion of BDNF, NGF, NT-3, NT-4, and GDNF by Müller cells. While solitary bands at approximately 13-14 kDa were observed for NGF, NT-3, and NT-4; two BDNF-reactive bands were observed in immunoblots: a faster migrating band at the reported size of the BDNF monomer (approximately 13 kDa); and a more intense band at approximately 36 kDa. GDNF-reactive bands were observed at approximately 22, approximately 28, and approximately 55 kDa. Glutamate also induced significant changes in glutamate receptor and transporter proteins, as well maintained the association of BDNF to TrkB in Müller cells. The decreased N-methyl-D-aspartate receptor (NMDAR) levels and sustained activation of TrkB by BDNF could serve as protective mechanisms for Müller cell survival. Moreover, the increased secretion of neurotrophic factors and upregulation of L-glutamate/L-aspartate transporter (GLAST) expression in Müller cells may protect retinal neurons from glutamate toxicity.
Sara Taylor; Bhooma Srinivasan; Robert J Wordinger; Rouel S Roque
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research. Molecular brain research     Volume:  111     ISSN:  0169-328X     ISO Abbreviation:  Brain Res. Mol. Brain Res.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-25     Completed Date:  2003-07-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8908640     Medline TA:  Brain Res Mol Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  189-97     Citation Subset:  IM    
Department of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
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MeSH Terms
Amino Acid Transport System X-AG / drug effects,  metabolism
Brain-Derived Neurotrophic Factor / metabolism,  secretion
Cells, Cultured
Glaucoma / metabolism*,  physiopathology
Glial Cell Line-Derived Neurotrophic Factor
Glutamic Acid / metabolism*,  pharmacology
Models, Biological
Nerve Growth Factor / metabolism,  secretion
Nerve Growth Factors / metabolism*,  secretion
Neuroglia / drug effects,  metabolism*,  secretion
Neurotoxins / metabolism*,  pharmacology
Neurotrophin 3 / metabolism,  secretion
Rats, Sprague-Dawley
Receptor, trkB / drug effects,  metabolism
Receptors, Glutamate / drug effects,  metabolism
Retina / metabolism*
Tetrazolium Salts / diagnostic use
Up-Regulation / drug effects*,  physiology
Reg. No./Substance:
0/Amino Acid Transport System X-AG; 0/Brain-Derived Neurotrophic Factor; 0/Gdnf protein, rat; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nerve Growth Factors; 0/Neurotoxins; 0/Neurotrophin 3; 0/Receptors, Glutamate; 0/Tetrazolium Salts; 143551-63-7/neurotrophin 4; 56-86-0/Glutamic Acid; 9061-61-4/Nerve Growth Factor; EC, trkB

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