Control of neuron outgrowth by NMDA receptors

The role of N-methyl-D-aspartic acid receptors (NMDARs) of glutamate on neu ritogenesis was studied in cultured neurons of chick embryo spinal cord usi ng the NMDAR non-competitive antagonist: dizocilpine maleate (MK-801). No c ell population was fully prevented from neuritogenesis by MK-801. Different aspects of neuritogenesis were quantitatively evaluated. Neurire initiatio n, elongation and branching were depressed by MK-801. Inhibition was dose-d ependent and reversible. A loss of responsiveness of neuritogenesis to MK-8 01 was found during the second day of treatment at a concentration of 10 mu M, but nor at higher concentrations. Our findings support the idea that Ca 2+ 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 excita tory 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 filopodi um-like processes in some of these cells.