The origin and nature of beading: a reversible transformation of the shape of nerve fibers.
Nerve fibers which appear beaded (varicose, spindle-shaped, etc.) are often considered the result of pathology, or a preparation artifact. However, beading can be promptly elicited in fresh normal nerve by a mild stretch and revealed by fast-freezing and freeze-substitution, or by aldehyde fixating at a temperature near 0 degree 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 compacted microtubules and neurofilaments. Labeled cytoskeletal proteins carried down by slow axonal transport are seen to move with the soluble components and not to have been incorporated into and remain with, the cytoskeletal organelles on beading the fibers. Lipids and other components of the myelin sheath are also shifted from the constrictions into the expansions, with preservation of its fine structure and thickness. Additionally, myelin intrusions into the axons are produced and a localized bulging into the axon termed "leafing". The beading constrictions do not arise from the myelin sheath: beading occurs in the axons of unmyelinated fibers. It does not depend on the axonal cytoskeleton: exposure of nerves in vitro to beta, beta'-iminodipropionitrile (IDPN) disaggregates the cytoskeletal organelles and even augments beading. The hypothesis advanced was that the beading constrictions are due to the membrane skeleton; the subaxolemmal network comprised of spectrin/fodrin, actin, ankyrin, integrins and other transmembrane proteins. The mechanism can be activated directly by neurotoxins, metabolic changes, and by an interruption of axoplasmic transport producing Wallerian degeneration.
Ochs
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Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.
Pourmand
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Jersild
R A
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Friedman
R N
RN
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003599:Cytoskeleton / Q000648:ultrastructure; D006801:Humans; D008959:Models, Neurological; D009186:Myelin Sheath / Q000648:ultrastructure; D009412:Nerve Fibers / Q000502:physiology* / Q000648:ultrastructure*; D015388:Organelles / Q000648:ultrastructure; D010812:Physical Stimulation