Delayed and isoform-specific effect of NMDA exposure on neural cell adhesion molecules in hippocampus

Brief stimulation of N-methyl-D-aspartate (NMDA) receptors has been shown to generate proteolytic fragments from the extracellular domain of neural cell adhesion molecules (NCAMs). In the present study, hippocampal slice cultures were used to demonstrate that such brief stimulation is followed by a delayed increase in the 180-kDa isoform NCAM-180. The slices were exposed to NMDA for 30 s followed by rapid quenching with the antagonist AP5. Immunoassays of the experimental samples indicated that concentrations of NCAM-180 were elevated above matched controls 2-3 h after the NMDA exposure, but not at earlier or later time points. This effect was isoform-specific as concentrations of the 140-kDa NCAM species were not found to increase. Interestingly, similar selectivity was evident with prolonged infusions of NMDA where, in contrast to the effect of brief stimulation, NCAM-180 content was reduced to 50% while levels of NCAM-140 were unchanged. Together with previous findings, the data indicate that the synaptic chemistries activated by NMDA differentially regulate NCAM-180 at the translation level and by localized activation of proteases.