The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration WldS nervesReportar como inadecuado

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BMC Neuroscience

, 6:6

First Online: 01 February 2005Received: 29 September 2004Accepted: 01 February 2005


BackgroundThe progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein YFP in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration Wld mutant mice.

ResultsIn wild-type nerves, we directly observed partially fragmented axons average 5.3% among a majority of fully intact or degenerated axons 37–42 h after transection and 40–44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all Wld axons were partially fragmented 15–25 days after nerve lesion, Wld axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks.

ConclusionsWe conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of trophic or regulatory factors by axonal transport triggers degeneration. Wld axons, once they finally degenerate, do so by a fundamentally different mechanism, indicated by differences in the rate, direction and abruptness of progression, and by different early morphological signs of degeneration. These observations suggest that Wld axons undergo a slow anterograde decay as axonal components are gradually depleted, and do not simply follow the degeneration pathway of wild-type axons at a slower rate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-6-6 contains supplementary material, which is available to authorized users.

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Autor: Bogdan Beirowski - Robert Adalbert - Diana Wagner - Daniela S Grumme - Klaus Addicks - Richard R Ribchester - Michael P 


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