Control of neuron outgrowth by NMDA receptors.
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.
Cuppini
R
R
Institute of Anatomy and Physiology, University of Urbino, Italy. r.cuppini@uniurb.it
Sartini
S
S
Ambrogini
P
P
Falcieri
E
E
Maltarello
M C
MC
Gallo
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002118:Calcium