PMID- 12654519
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20220310
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 111
IP  - 1-2
DP  - 2003 Mar 17
TI  - Glutamate stimulates neurotrophin expression in cultured Muller cells.
PG  - 189-97
AB  - 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 Muller 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 Muller 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 Muller 
      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 Muller cells. The 
      decreased N-methyl-D-aspartate receptor (NMDAR) levels and sustained activation 
      of TrkB by BDNF could serve as protective mechanisms for Muller cell survival. 
      Moreover, the increased secretion of neurotrophic factors and upregulation of 
      L-glutamate/L-aspartate transporter (GLAST) expression in Muller cells may 
      protect retinal neurons from glutamate toxicity.
FAU - Taylor, Sara
AU  - Taylor S
AD  - Department of Cell Biology and Genetics, University of North Texas Health Science 
      Center, Fort Worth, TX 76107, USA.
FAU - Srinivasan, Bhooma
AU  - Srinivasan B
FAU - Wordinger, Robert J
AU  - Wordinger RJ
FAU - Roque, Rouel S
AU  - Roque RS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotoxins)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Tetrazolium Salts)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Amino Acid Transport System X-AG/drug effects/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Glaucoma/*metabolism/physiopathology
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Glutamic Acid/*metabolism/pharmacology
MH  - Models, Biological
MH  - Nerve Growth Factor/metabolism
MH  - Nerve Growth Factors/*metabolism
MH  - Neuroglia/drug effects/*metabolism
MH  - Neurotoxins/*metabolism/pharmacology
MH  - Neurotrophin 3/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/drug effects/metabolism
MH  - Receptors, Glutamate/drug effects/metabolism
MH  - Retina/*metabolism
MH  - Tetrazolium Salts
MH  - Up-Regulation/*drug effects/physiology
EDAT- 2003/03/26 05:00
MHDA- 2003/07/17 05:00
CRDT- 2003/03/26 05:00
PHST- 2003/03/26 05:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2003/03/26 05:00 [entrez]
AID - S0169328X03000305 [pii]
AID - 10.1016/s0169-328x(03)00030-5 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2003 Mar 17;111(1-2):189-97. doi: 
      10.1016/s0169-328x(03)00030-5.