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Articles

Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons

MP Mattson, KN Kumar, H Wang, B Cheng and EK Michaelis
Journal of Neuroscience 1 November 1993, 13 (11) 4575-4588; DOI: https://doi.org/10.1523/JNEUROSCI.13-11-04575.1993
MP Mattson
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KN Kumar
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H Wang
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B Cheng
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EK Michaelis
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Abstract

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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The Journal of Neuroscience: 13 (11)
Journal of Neuroscience
Vol. 13, Issue 11
1 Nov 1993
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Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons
MP Mattson, KN Kumar, H Wang, B Cheng, EK Michaelis
Journal of Neuroscience 1 November 1993, 13 (11) 4575-4588; DOI: 10.1523/JNEUROSCI.13-11-04575.1993

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Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons
MP Mattson, KN Kumar, H Wang, B Cheng, EK Michaelis
Journal of Neuroscience 1 November 1993, 13 (11) 4575-4588; DOI: 10.1523/JNEUROSCI.13-11-04575.1993
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