| | |  | | | | Record from Web of Science® | | | | | | |
| BASIC FGF REGULATES THE EXPRESSION OF A FUNCTIONAL 71-KDA NMDA RECEPTOR PROTEIN THAT MEDIATES CALCIUM INFLUX AND NEUROTOXICITY IN HIPPOCAMPAL-NEURONS |
|
|
| Author(s): MATTSON MP, KUMAR KN, WANG H, CHENG B, MICHAELIS EK |
| Source: JOURNAL OF NEUROSCIENCE Volume: 13 Issue: 11 Pages: 4575-4588 Published: NOV 1993 |
| Times Cited: 151 References: 64 |
| 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 excitotoxic/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-7 1. 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: MATTSON, MP (reprint author), UNIV KENTUCKY, SANDERS BROWN RES CTR AGING, 800 S LIMESTONE, LEXINGTON, KY 40536 USA |
Addresses:
1. UNIV KENTUCKY, DEPT ANAT & NEUROBIOL, LEXINGTON, KY 40536 USA
2. UNIV KANSAS, DEPT PHARMACOL & TOXICOL, LAWRENCE, KS 66045 USA
3. UNIV KANSAS, CTR BIOMED RES, LAWRENCE, KS 66045 USA |
| Publisher: SOC NEUROSCIENCE, 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 |
| Subject Category: Neurosciences |
| IDS Number: MF297 |
| ISSN: 0270-6474 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |