Loss of the compound action potential: an electrophysiological, biochemical and morphological study of early events in axonal degeneration in the C57BL/Ola mouse.
In the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration--Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium-activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1-month-old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post-transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice. In vitro and in vivo degeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid decline in vitro than in vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had > 50% of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane--a transected nerve becomes unable to conduct a compound action potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Oxford, UK.
J W
JW
Tsao
M C
MC
Brown
M J
MJ
Carden
W G
WG
McLean
V H
VH
Perry
D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000032:analysis; D012584:Sciatic Nerve / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D013045:Species Specificity; D014855:Wallerian Degeneration / Q000235:genetics / Q000502:physiology*
D016900:Neurofilament Proteins