THE ORIGIN AND NATURE OF BEADING - A REVERSIBLE TRANSFORMATION OF THESHAPE OF NERVE-FIBERS

Nerve fibers which appear beaded (varicose, spindle-shaped, etc.) are often considered the result of pathology, or a preparation artifact. H owever, beading can be promptly elicited in fresh normal nerve by a mi ld stretch and revealed by fast-freezing and freeze-substitution, or b y aldehyde fixating at a temperature near 0 degrees C (cold-fixation). The key change in beading are the constrictions, wherein the axon is much reduced in diameter. Axoplasmic fluid and soluble components are shifted from the constrictions into the expansions leaving behind comp acted microtubules and neurofilaments. Labeled cytoskeletal proteins c arried down by slow axonal transport are seen to move with the soluble components and not to have been incorporated into, and remain with, t he cytoskeletal organelles on beading the fibers.Lipids and other comp onents of the myelin sheath are also shifted from the constrictions in to the expansions, with preservation of its fine structure and thickne ss. Additionally, myelin intrusions into the axons are produced and a localized bulging into the axon termed ''leafing'', The beading constr ictions do not arise from the myelin sheath: beading occurs in the axo ns of unmyelinated fibers. It does not depend on the axonal cytoskelet on: exposure of nerves in vitro to beta,beta'-iminodi-propionitrile (I DPN) disaggregates the cytoskeletal organelles and even augments beadi ng. The hypothesis advanced was that the beading constrictions are due to the membrane skeleton; the subaxolemmal network comprised of spect rin/fodrin, actin, ankyrin, integrins and other transmembrane proteins . The mechanism can be activated directly by neurotoxins, metabolic ch anges, and by an interruption of axoplasmic transport producing Waller ian degeneration. (C) 1997 Elsevier Science Ltd.