 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, October 1, 1998, 18(19):7953-7961
Brain-Derived Neurotrophic Factor and Basic Fibroblast Growth Factor Downregulate NMDA Receptor Function in Cerebellar Granule Cells
Cinzia Brandoli1, Angela Sanna1, Maria A. De Bernardi2, Paolo Follesa1, Gary Brooker2, and Italo Mocchetti1 1 Department of Cell Biology, Division of Neurobiology, Georgetown University, School of Medicine, Washington, DC 20007, and 2 Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218
Evidence has accumulated to suggest that the NMDA glutamate receptor subtype plays an important role in neuronal degeneration evoked by hypoxia, ischemia, or trauma. Cerebellar granule cells in culture are vulnerable to NMDA-induced neuronal excitotoxicity. In these cells, brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF2) prevent the excitotoxic effect of NMDA. However, little is known about the molecular mechanisms underlying the protective properties of these trophic factors. Using cultured rat cerebellar granule cells, we investigated whether BDNF and FGF2 prevent NMDA toxicity by downregulating NMDA receptor function. Western blot and RNase protection analyses were used to determine the expression of the various NMDA receptor subunits (NR1, NR2A, NR2B, and NR2C) after BDNF or FGF2 treatment. FGF2 and BDNF elicited a time-dependent decrease in the expression of NR2A and NR2C subunits. Because NMDA receptor activation leads to increased intracellular Ca2+ concentration ([Ca2+]i), we studied the effect of the BDNF- and FGF2-induced reduction in NR2A and NR2C synthesis on the NMDA-evoked Ca2+ responses by single-cell fura-2 fluorescence ratio imaging. BDNF and FGF2 reduced the NMDA-mediated [Ca2+]i increase with a time dependency that correlates with their ability to decrease NR2A and NR2C subunit expression, suggesting that these trophic factors also induce a functional downregulation of the NMDA receptor. Because sustained [Ca2+]i is believed to be causally related to neuronal injury, we suggest that BDNF and FGF2 may protect cerebellar granule cells against excitotoxicity by altering the NMDA receptor-Ca2+ signaling via a downregulation of NMDA receptor subunit expression.
Key words: BDNF; FGF2; glutamate; NMDA receptor subunits; NR1; NR2A; Ca2+
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197953-09$05.00/0
This article has been cited by other articles:
T. W. Weiss, A. L. Samson, B. Niego, P. B. Daniel, and R. L. Medcalf
Oncostatin M is a neuroprotective cytokine that inhibits excitotoxic injury in vitro and in vivo
FASEB J, November 1, 2006; 20(13): 2369 - 2371.
[Abstract] [Full Text] [PDF]
F. T. Khasawneh, J.-S. Huang, J. W. Turek, and G. C. L. Breton
Differential Mapping of the Amino Acids Mediating Agonist and Antagonist Coordination with the Human Thromboxane A2 Receptor Protein
J. Biol. Chem., September 15, 2006; 281(37): 26951 - 26965.
[Abstract] [Full Text] [PDF]
S. Nakanishi and M. Okazawa
Membrane potential-regulated Ca2+ signalling in development and maturation of mammalian cerebellar granule cells
J. Physiol., September 1, 2006; 575(2): 389 - 395.
[Abstract] [Full Text] [PDF]
A. Bachis, S. A. Aden, R. L. Nosheny, P. M. Andrews, and I. Mocchetti
Axonal transport of human immunodeficiency virus type 1 envelope protein glycoprotein 120 is found in association with neuronal apoptosis.
J. Neurosci., June 21, 2006; 26(25): 6771 - 6780.
[Abstract] [Full Text] [PDF]
A. Bachis, E. O. Major, and I. Mocchetti
Brain-Derived Neurotrophic Factor Inhibits Human Immunodeficiency Virus-1/gp120-Mediated Cerebellar Granule Cell Death by Preventing gp120 Internalization
J. Neurosci., July 2, 2003; 23(13): 5715 - 5722.
[Abstract] [Full Text] [PDF]
S. J. Rabin, A. Bachis, and I. Mocchetti
Gangliosides Activate Trk Receptors by Inducing the Release of Neurotrophins
J. Biol. Chem., December 13, 2002; 277(51): 49466 - 49472.
[Abstract] [Full Text] [PDF]
A. Bachis, A. M. Colangelo, S. Vicini, P. P. Doe, M. A. De Bernardi, G. Brooker, and I. Mocchetti
Interleukin-10 Prevents Glutamate-Mediated Cerebellar Granule Cell Death by Blocking Caspase-3-Like Activity
J. Neurosci., May 1, 2001; 21(9): 3104 - 3112.
[Abstract] [Full Text] [PDF]
D. M. O'Dell, R. Raghupathi, P. B. Crino, J. H. Eberwine, and T. K. McIntosh
Traumatic Brain Injury Alters the Molecular Fingerprint of TUNEL-Positive Cortical Neurons In Vivo: A Single-Cell Analysis
J. Neurosci., July 1, 2000; 20(13): 4821 - 4828.
[Abstract] [Full Text] [PDF]
C. Tiruppathi, W. Yan, R. Sandoval, T. Naqvi, A. N. Pronin, J. L. Benovic, and A. B. Malik
G protein-coupled receptor kinase-5 regulates thrombin-activated signaling in endothelial cells
PNAS, June 20, 2000; 97(13): 7440 - 7445.
[Abstract] [Full Text] [PDF]
A. El Idrissi and E. Trenkner
Growth Factors and Taurine Protect against Excitotoxicity by Stabilizing Calcium Homeostasis and Energy Metabolism
J. Neurosci., November 1, 1999; 19(21): 9459 - 9468.
[Abstract] [Full Text] [PDF]
N. Chen, T. Luo, and L. A. Raymond
Subtype-Dependence of NMDA Receptor Channel Open Probability
J. Neurosci., August 15, 1999; 19(16): 6844 - 6854.
[Abstract] [Full Text] [PDF]
Y. D. Teng, I. Mocchetti, A. M. Taveira-DaSilva, R. A. Gillis, and J. R. Wrathall
Basic Fibroblast Growth Factor Increases Long-Term Survival of Spinal Motor Neurons and Improves Respiratory Function after Experimental Spinal Cord Injury
J. Neurosci., August 15, 1999; 19(16): 7037 - 7047.
[Abstract] [Full Text] [PDF]
A. M. Marini, S. J. Rabin, R. H. Lipsky, and I. Mocchetti
Activity-dependent Release of Brain-derived Neurotrophic Factor Underlies the Neuroprotective Effect of N-Methyl-D-aspartate
J. Biol. Chem., November 6, 1998; 273(45): 29394 - 29399.
[Abstract] [Full Text] [PDF]
N. O. Dulin, P. Pratt, C. Tiruppathi, J. Niu, T. Voyno-Yasenetskaya, and M. J. Dunn
Regulator of G Protein Signaling RGS3T Is Localized to the Nucleus and Induces Apoptosis
J. Biol. Chem., July 7, 2000; 275(28): 21317 - 21323.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|