Platelet-derived growth factor selectively inhibits NR2B-containing N-methyl-D-aspartate receptors in CA1 hippocampal neurons.

Academic Article


  • Platelet-derived growth factor (PDGF) beta receptor activation inhibits N-methyl-d-aspartate (NMDA)-evoked currents in hippocampal and cortical neurons via the activation of phospholipase Cgamma, PKC, the release of intracellular calcium, and a rearrangement of the actin cytoskeleton. In the hippocampus, the majority of NMDA receptors are heteromeric; most are composed of 2 NR1 subunits and 2 NR2A or 2 NR2B subunits. Using NR2B- and NR2A-specific antagonists, we demonstrate that PDGF-BB treatment preferentially inhibits NR2B-containing NMDA receptor currents in CA1 hippocampal neurons and enhances long-term depression in an NR2B subunit-dependent manner. Furthermore, treatment of hippocampal slices or cultures with PDGF-BB decreases the surface localization of NR2B but not of NR2A subunits. PDGFbeta receptors colocalize to a higher degree with NR2B subunits than with NR2A subunits. After neuronal injury, PDGFbeta receptors and PDGF-BB are up-regulated and PDGFbeta receptor activation is neuroprotective against glutamate-induced neuronal damage in cultured neurons. We demonstrate that the neuroprotective effects of PDGF-BB are occluded by the NR2B antagonist, Ro25-6981, and that PDGF-BB promotes NMDA signaling to CREB and ERK1/2. We conclude that PDGFbetaR signaling, by preferentially targeting NR2B receptors, provides an important mechanism for neuroprotection by growth factors in the central nervous system.
  • Authors

  • Beazely, Michael A
  • Lim, Aeni
  • Li, Hongbin
  • Trepanier, Catherine
  • Chen, Xuanmao
  • Sidhu, Bikram
  • Macdonald, John F
  • Status

    Publication Date

  • March 20, 2009
  • Published In


  • Actins
  • Animals
  • Becaplermin
  • Calcium
  • Cyclic AMP Response Element-Binding Protein
  • Cytoskeleton
  • Hippocampus
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • N-Methylaspartate
  • Neurons
  • Phenols
  • Phospholipase C gamma
  • Piperidines
  • Platelet-Derived Growth Factor
  • Protein Kinase C
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Rats, Wistar
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, N-Methyl-D-Aspartate
  • Signal Transduction
  • Digital Object Identifier (doi)

    Start Page

  • 8054
  • End Page

  • 8063
  • Volume

  • 284
  • Issue

  • 12