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 t o generate proteolytic fragments from the extracellular domain of neural ce ll adhesion molecules (NCAMs). In the present study, hippocampal slice cult ures 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 t o NMDA for 30 s followed by rapid quenching with the antagonist AP5. Immuno assays of the experimental samples indicated that concentrations of NCAM-18 0 were elevated above matched controls 2-3 h after the NMDA exposure. but n ot at earlier or later time points. This effect was isoform-specific as con centrations of the 140-kDa NCAM species were not found to increase. Interes tingly, similar selectivity was evident with prolonged infusions of NMDA wh ere, in contrast to the effect of brief stimulation, NCAM-180 content was r educed to 50% while levels of NCAM-140 were unchanged. Together with previo us findings, the data indicate that the synaptic chemistries activated by N MDA differentially regulate NCAM-180 at the translation level and by locali zed activation of proteases. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.