Rapid expression and transport of embryonic N‐CAM in dentate gyrus following entorhinal cortex lesion: Ultrastructural analysis

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Abstract
Neural cell adhesion molecules are known to be important in axon guidance 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‐CAM 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 hours post‐ERC lesion) were stained with anti‐eN‐CAM and processed for immunoelectron 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 staining, and dendritic cytoplasm was heavily labeled. Twenty‐four hours following lesion, plasma membrane staining of eN‐CAM on both axons and dendrites had increased in intensity within the OML, whereas membrane eN‐CAM staining was diminished in the inner molecular layer (IML), and the intradendritic cytoplasmic staining disappeared. By 48 hours after lesion, eN‐CAM staining had disappeared from the IML but remained intense and widely distributed in the OML. These findings suggest a rapid transport of de novo synthesized protein. A generalized reaction appears to occur immediately following denervation, and eN‐CAM is up‐regulated in the complete expanse of the dendritic membrane, despite the fact that only the OML is denervated. The newly up‐regulated eN‐CAM is rapidly withdrawn or disappears from the membrane in the (nondenervated) IML over the 24–48 hours postlesion. The brain rapidly responds to injury at the cellular level in the denervated zone in preparation for renervation by axon sprouting.