Control of neuron outgrowth by NMDA receptors

J Submicrosc Cytol Pathol. 1999 Jan;31(1):31-40.

Abstract

The role of N-methyl-D-aspartic acid receptors (NMDARs) of glutamate on neuritogenesis was studied in cultured neurons of chick embryo spinal cord using the NMDAR non-competitive antagonist dizocilpine maleate (MK-801). No cell population was fully prevented from neuritogenesis by MK-801. Different aspects of neuritogenesis were quantitatively evaluated. Neurite initiation, elongation and branching were depressed by MK-801. Inhibition was dose-dependent and reversible. A loss of responsiveness of neuritogenesis to MK-801 was found during the second day of treatment at a concentration of 10 microM, but not at higher concentrations. Our findings support the idea that Ca2+ influx through NMDAR associated channels is one of the possible triggers of a cascade resulting in neuritogenesis. The effects of NMDAR blocking on neuritogenesis occurred before synaptogenesis, suggesting a role of excitatory aminoacids in neuron morphological differentiation at early stages of development. Scanning electron microscopy confirmed a reduction in neurite tree complexity in MK-801 treated cells and showed a production of filopodium-like processes in some of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Chick Embryo
  • Dizocilpine Maleate / pharmacology*
  • Microscopy, Electron, Scanning
  • Neurites / drug effects
  • Neurites / physiology*
  • Neurites / ultrastructure
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Spinal Cord / cytology*
  • Spinal Cord / physiology

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Calcium