Expression of polysialylated NCAM but not L1 or N-cadherin by regeneratingadult mouse optic fibers in vitro

This study asks if there might be irreversible maturational changes in adul t neurons that limit their capacity to regenerate. Retina from adult and em bryonic mouse were placed in culture on laminin substrates so that regenera ting adult optic fibers could be compared to growing embryonic fibers. Seve ral 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 exam ined. As in vivo, embryonic fibers were found to express both L1 and N-cadh erin. in contrast, regenerating adult fibers had no detectable amounts of e ither of these CAMs. N-Cadherin is normally down regulated during developme nt 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 regen erating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally foun d in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, which in vivo is normally found in embryonic and at lower levels in a dult fibers. Surprisingly, both embryonic and regenerating adult fibers exp ressed high levels of polysialic acid, which is normally absent in adult fi bers. NCAM may be one of few CAMs available to adult optic fibers for regen eration on astrocytes. (C) 1999 Academic Press.