Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons
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Issue Date
1993-11-01Author
Mattson, Mark P.
Kumar, Keshava N.
Wang, Hong
Cheng, Bin
Michaelis, Elias K.
Publisher
Society for Neuroscience
Type
Article
Article Version
Scholarly/refereed, publisher version
Published Version
http://www.jneurosci.org/content/13/11/4575Metadata
Show full item recordAbstract
Basic fibroblast growth factor (bFGF) was recently found to modulate the outgrowth-regulating effects of glutamate, and protected neurons from several brain regions against excitotoxi/ischemic damage. We provide evidence that the excitoprotective mechanism of bFGF involves suppression of the expression of a 71 kDa NMDA receptor protein (NMDARP- 71). NMDARP-71 protein and mRNA levels were reduced in neurons in bFGF- treated hippocampal cell cultures. The levels of the NMDARP-71 were not reduced by NGF or epidermal growth factor, and bFGF did not reduce the level of mRNA for the GluR1 kainate/AMPA receptor, demonstrating the specificity of the effect of bFGF on the NMDARP-71. The reduction in NMDARP-71 expression in bFGF-treated neurons was correlated with reduced vulnerability to NMDA neurotoxicity. A major role for NMDARP-71 in calcium responses to NMDA and excitotoxicity was demonstrated using antisense oligonucleotides directed against NMDARP-71. Northern and Western blot analysis and immunocytochemistry showed that NMDARP-71 antisense oligonucleotides caused a selective suppression of NMDARP-71 mRNA and protein levels during 12–44 hr exposure periods. Elevations in intracellular calcium levels normally caused by glutamate and NMDA were attenuated in neurons exposed to NMDARP-71 antisense oligonucleotide; calcium responses to kainate were relatively unaffected. NMDARP-71 antisense oligonucleotides protected the neurons against excitotoxicity. Thus, NMDARP-71 is a necessary component of an NMDA receptor mediating calcium responses and neurotoxicity in hippocampal neurons. Taken together, these data identify a mechanism whereby bFGF can modify neuronal responses to glutamate, and suggest that regulating the expression of excitatory amino acid receptors may provide a means for growth factors to influence the plasticity and degeneration of neural circuits.
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This is the publisher's version, also available electronically from "http://www.jneurosci.org".
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- Pharmacy Scholarly Works [293]
Citation
Mattson, M. P., Kumar, K. N., Wang, H., Cheng, B. & Michaelis, E. K. (1993) Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons. Journal of Neuroscience, 13(11), 4575-4588.
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