Embryonic neural cell adhesion molecule (N-CAM) is elevated in the denervated rat dentate gyrus

Abstract

We evaluated the immunohistological changes in neural cell adhesion molecule (N-CAM) expression in the adult rat dentate gyrus during the period of synaptic degeneration, axonal sprouting, and synaptogenesis following ipsilateral entorhinal cortex (ERC) lesion. This lesion denervates the outer two-thirds of the dentate granule cells dendrites and induces compensatory sprouting from the subjacent inner one-third into the denervated zone, as well as reactive synaptogenesis in the denervated outer molecular layer. In unlesioned adult hippocampus, antibodies to total N-CAM stained the inner molecular layer intensely, and the outer molecular layer (ML) more lightly. After ERC lesion the intense staining of the inner layer widened, the expansion following the known temporal sequence of commissural and associational (C/A) axon sprouting into the denervated zone. In normal unlesioned controls there was very light, uniform staining of the ML with antibodies directed against embryonic N-CAM (eN-CAM). By 2 d post-ERC lesion, the outer two-thirds of the ML stained robustly with antibody to eN-CAM. This area of intense staining receded as the C/A axon collaterals from the inner one-third entered the denervated zone, so that by 30 d the intense eN-CAM staining only occupied the outer half of the ML. The increased expression of eN-CAM remained present at 60 d post-ERC lesion, past the point that synaptic volume density has returned to normal levels in the denervated zone. Ultrastructural studies showed that the newly expressed eN-CAM was located on the surface of dendrites in the denervated zone, but was not found at the synaptic contacts. It was seen on the regenerating axons as well. These studies allow us to compare temporal and spatial correspondence between the expression of eN-CAM and the known sequence of reactive synaptogenesis and axonal sprouting in the dentate gyrus. Our findings indicate that neural cell adhesion molecules are important in the dendritic response to sprouting and synaptic remodeling. Reexpression of eN-CAM in the denervated zone is an important component of such axon-dendrite interactions in the CNS. Where reinnervation of the proximal dendritic field of the OML is by axons of the sprouting C/A afferents, eN-CAM is no longer expressed in the wake of the translaminar expansion. The outer ML, which is reinnervated by other afferents, maintains high levels of eN-CAM when reinnervation is complete. Thus, the source of the reinnervating axons determines the response of the dendritic membrane of the target neurons.