An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system

This work was prompted by the accidental observation that a newly developed , affinity purified polyclonal antibody against the C-terminus of the neuro peptide tyrosine (NPY) Y1-receptor protein decorates degenerating fibers in the central nervous system (CNS). This staining did not appear in control animals in which the antibody marked perikarya and dendrites at previously described locations [X. Zhang, L. Bao, Z.-Q. Xu, J. Kopp, U. Arvidsson, R. Elde, T. Hokfelt, Localization of neuropeptide Y Y1-receptors in the rat ne rvous system with special reference to somatic receptors on small dorsal ro ot ganglion neurons, Proc. Natl. Acad. Sci. USA 91 (1994) 11738-11742]. Thr ee models of experimental lesions were studied: sciatic nerve transection, spinal cord transection and parietal cortex thermocoagulation. In each mode l, animals were divided in groups (n = 2) and processed for indirect immuno fluorescence at different time intervals up to 28 days post-lesion (PL) (se e below). All three experimental lesions produced a very intense immunolabe ling of fibers in the projection pathways of the lesioned structures, stron gly reminding of Wallerian degeneration (WD). In the sciatic nerve, the sta ining first appeared on day 1 PL, was strongly increased on day 3 PL, then declined after 7 days and had almost completely disappeared after 14 days. In the CNS, the staining appeared later and was first observed on day 3 PL and remained for a longer period, thus showing different time courses in th e brain and spinal cord as compared to the sciatic nerve. The labeling was completely abolished, both in the CNS and in the sciatic nerve, by pre-incu bation of the Y1-R antibody with the immunogenic peptide at a dilution of 1 0(-6) M. The appearance of the staining and its time course strongly sugges t that the process was related to degenerating axons. Although the protein actually detected remains to be determined, it is suggested that the staini ng ability of this antibody could be used as a positive marker of axonal de generation following experimental or naturally occurring lesions of the ner vous system. (C) 1999 Elsevier Science B.V. All rights reserved.