RAPID EXPRESSION AND TRANSPORT OF EMBRYONIC N-CAM IN DENTATE GYRUS FOLLOWING ENTORHINAL CORTEX LESION - ULTRASTRUCTURAL ANALYSIS

Neural cell adhesion molecules are known to be important in axon guida nce and synapse formation in the developing brain. The embryonic form of neural cell adhesion molecule (eN-CAM) is reexpressed in the outer molecular layer (OML) of the dentate gyrus following entorhinal cortex (ERC) lesion. Ultrastructural analysis revealed localization of eN-CA M to the membrane of granule-cell dendritic membranes and occasionally axons within the denervated zone. Because eN-CAM is expressed rapidly (within 2 days) after ERC lesion, we were interested in the temporal sequence of expression. Denervated hippocampi (12, 15, 24, and 48 hour s post-ERC lesion) were stained with anti-eN-CAM and processed for imm unoelectron microscopy. At 12 hours, there was no evidence of staining for eN-CAM. By 15 hours after lesion, membranes of both dendrites and axons throughout the molecular layer exhibited moderate eN-CAM staini ng, and dendritic cytoplasm was heavily labeled. Twenty-four hours fol lowing lesion, plasma membrane staining of eN-CAM on both axons and de ndrites had increased in intensity within the OML, whereas membrane eN -CAM staining was diminished in the inner molecular layer (IML), and t he intradendritic cytoplasmic staining disappeared. By 48 hours after lesion, eN-CAM staining had disappeared from the IML but remained inte nse and widely distributed in the OML. These findings suggest a rapid transport of de novo synthesized protein. A generalized reaction appea rs to occur immediately following denervation, and eN-CAM is up-regula ted in the complete expanse of the dendritic membrane, despite the fac t that only the OML is denervated. The newly up-regulated eN-CAM is ra pidly withdrawn or disappears from the membrane in the (nondenervated) IML over the 24-48 hours postlesion. The brain rapidly responds to in jury at the cellular level in the denervated zone in preparation for r enervation by axon sprouting. (C) 1994 Wiley-Liss, Inc.