Peptide accumulations in proximal endbulbs of transected axons

Axons proximal to a transection develop into enlarged, but presumed 'passiv e' endbulb structures. In previous studies, we observed that proximal stump s of transected sciatic nerves accumulate discrete and striking deposits of calcitonin gene-related peptide (CGRP) that have apparent direct and local actions on nearby microvessels. In this work, we provide evidence that CGR P, in the company of several additional peptides, are deposited through 'ar rested' anterograde transport into axon endbulbs that develop after transec tion. In proximal stump tips of rat sciatic nerves transected 48 h earlier, CGRP accumulation colocalized with a label for neurofilament that was acce ntuated at axon tips, but was prevented by a concurrent more proximal sciat ic section. Similarly, interruption of CGRP deposition eliminated its appar ent actions on local microvessels following injury. CGRP accumulation was a lso observed in sural nerve proximal stump tips, indicating its presence in sensory axons despite the known declines in the sensory neuronal synthesis of CGRP that occur following axotomy. Peptide accumulation was not unique to CGRP, with a similar pattern of anterograde accumulation observed for su bstance P (SP), neuropeptide Y (NPY) and galanin. Deposited peptides and pe rhaps other axonal constituents in the milieu of a peripheral nerve injury may be associated with important local physiological actions in the regener ative microenvironment. (C) 2001 Published by Elsevier Science B.V.