Expression of Polysialylated NCAM but Not L1 orN-Cadherin by Regenerating Adult Mouse Optic Fibersin Vitro

Abstract

This study asks if there might be irreversible maturational changes in adult neurons that limit their capacity to regenerate. Retina from adult and embryonic mouse were placed in culture on laminin substrates so that regenerating adult optic fibers could be compared to growing embryonic fibers. Several cell adhesion molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes were assayed by immunocytochemistry: L1,N-cadherin, and NCAM. Thy 1.2, a potential CAM with inhibitory activity, was also examined. Asin vivo,embryonic fibers were found to express both L1 andN-cadherin. In contrast, regenerating adult fibers had no detectable amounts of either of these CAMs.N-Cadherin is normally down regulated during development so its absence in adult fibers suggests it can not be reexpressed during regeneration. L1 is normally found in the proximal regions of adult optic fibers so its absence indicates it is not expressed or transported in regenerating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, whichin vivois normally found in embryonic and at lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult fibers expressed high levels of polysialic acid, which is normally absent in adult fibers. NCAM may be one of few CAMs available to adult optic fibers for regeneration on astrocytes.