Kb. Hoffman et al., Delayed and isoform-specific effect of NMDA exposure on neural cell adhesion molecules in hippocampus, NEUROSCI RE, 39(2), 2001, pp. 167-173
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.