Degeneration of neuronal cell bodies following axonal injury in Wld(S) mice.
The phenotype of Wld(S) ("slow Wallerian degeneration") mice demonstrates prolonged survival of injured axons. However, whether the Wld(S) mutation delays degeneration of the neuronal cell body following axonal injury is unclear. We used a retrograde model of axonal transport failure in Wld(S) mice to test whether the mutant Wld(S) protein has any beneficial effect on the neuronal cell body. Retrograde axonal transport was physically blocked by optic nerve crush and confirmed by the absence of Fluoro-Gold labeling in wild-type and in Wld(S) mice. After this axonal injury, there was marked protection of axonal degeneration in the Wld(S) phenotype, as confirmed by immunohistochemistry and electron microscopy. However, the Wld(S) protein, localized in the nucleus of retinal ganglion cells, did not prevent or delay degeneration of the retinal ganglion cell body, confirmed by TUNEL staining and Fluoro-Gold labeling. These results imply that, after axonal injury, Wallerian degeneration of axons and degeneration of the neuronal cell body have different mechanisms, which are autonomous and independent of each other. Although the Wld(S) phenotype can be used to demonstrate stable enucleate axons, the mutation is unlikely to protect neurons in neurodegenerative diseases in which there is failure of retrograde transport.
Wang
Ai Ling
AL
Laboratory for the Investigation of the Aging Retina, Department of Ophthalmology, Northwestern University School of Medicine, Chicago, IL 60611, USA. a-wang@northwestern.edu
Yuan
Ming
M
Neufeld
Arthur H
AH
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000235:genetics / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors; D014855:Wallerian Degeneration / Q000235:genetics*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D013266:Stilbamidines; C442580:Wld protein, mouse; C050934:neurofilament protein 150