RT Journal Article
SR Electronic
T1 Temperature Modulation Reveals Three Distinct Stages of Wallerian Degeneration
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4718
OP 4726
DO 10.1523/JNEUROSCI.19-12-04718.1999
VO 19
IS 12
A1 Tsao , Jack W.
A1 George, Edwin B.
A1 Griffin, John W.
YR 1999
UL http://www.jneurosci.org/content/19/12/4718.abstract
AB After peripheral nerve transection, axons distal to the cut site rapidly degenerate, a process termed Wallerian degeneration. In wild-type mice the compound action potential (CAP) disappears by 3 d. Previous studies have demonstrated that cold temperatures and lower extracellular calcium ion (Ca2+) concentrations can slow the rate of Wallerian degeneration. We have incubated isolated sciatic nerve segments from wild-type and C57BL/Wld mice (which carry a gene slowing Wallerian degeneration) in vitro at 25 and 37°C. At 25°C we found that the degeneration rate of wild-type axons was slowed dramatically, with the CAP preserved up to 7 d post-transection. In contrast, at 37°C the CAPs were minimal at 2 d. When the temperature of wild-type nerves was raised to 37°C after 24–72 hr at 25°C, degeneration occurred within the subsequent 24 hr. Wld nerves, too, were preserved longer at 25°C but, on return to 37°C, degenerated promptly. Cooling the nerve within 12 hr after axotomy enhanced axonal preservation. Neither wild-type nor Wld nerves showed different degeneration rates when they were incubated with 250 μm or 5 or 10 mm extracellular Ca2+ for 1–2 d, suggesting that an abrupt increase in intracellular Ca2+ occurs at the time of axonal destruction. Wallerian degeneration, thus, appears to progress through three distinct stages. Initiation occurs at the time of injury with subsequent temperature-dependent and -independent phases. Nerves appear to remain intact and are able to exclude Ca2+ from entering until an as yet unknown process finally increases axolemmal permeability.