Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortex

Eur J Neurosci. 2006 Aug;24(3):645-53. doi: 10.1111/j.1460-9568.2006.04957.x. Epub 2006 Jul 18.


Excitatory amino acids such as glutamate play important roles in the central nervous system. We previously demonstrated that a neurosteroid, dehydroepiandrosterone (DHEA), has powerful effects on the cell proliferation of human neural progenitor cells (hNPC) derived from the fetal cortex, and this effect is modulated through NMDA receptor signaling. Here, we show that glutamate can significantly increase the proliferation rates of hNPC. The increased proliferation could be blocked by specific NMDA receptor antagonists, but not other glutamate antagonists for kainate-AMPA or metabotropic receptors. The NR1 subunit of the NMDA receptor was detectable in elongated bipolar or unipolar cells with small cell bodies. These NR1-positive cells were colocalized with GFAP immunoreactivity. Detection of the phosphorylation of cAMP response element-binding protein (pCREB) revealed that a subset of NR1-positive hNPC could respond to glutamate. Furthermore, we hypothesized that glutamate treatment may affect mainly the hNPC with a radial morphology and found that glutamate as well as DHEA selectively affected elongated hNPC; these elongated cells may be a type of radial glial cell. Finally we asked whether the glutamate-responsive hNPC had an increased potential for neurogenesis and found that glutamate-treated hNPC produced significantly more neurons following differentiation. Together these data suggest that glutamate stimulates the division of human progenitor cells with neurogenic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Proliferation / drug effects*
  • Cell Shape / drug effects
  • Cell Shape / physiology
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / embryology
  • Central Nervous System / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Humans
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Cyclic AMP Response Element-Binding Protein
  • Excitatory Amino Acid Antagonists
  • Glial Fibrillary Acidic Protein
  • NR1 NMDA receptor
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid