Neurites undergoing Wallerian degeneration show an apoptotic-like process with Annexin V positive staining and loss of mitochondrial membrane potential.
Wallerian degeneration, the disintegration of the distal part of an injured axon, is an important event in many neurodegenerative diseases. We studied Wallerian degeneration in dorsal root ganglion (DRG) explants in culture by separating neurites from their cell bodies with a scalpel. The severed neurites showed Annexin V positive staining, that spreads distally with a rate comparable to that of slow axonal transport in intact neurons in vivo. Moreover, the injured neurites showed loss of mitochondrial membrane potential. These features resemble those seen when cells undergo apoptosis. These data contribute to a new understanding of the mechanism of axonal degeneration, have implications for the response of stromal cells in central nervous system (CNS) and raise the prospect of new pharmacological treatments for those neurodegenerative pathologies where the protection of the cell body alone does not alleviate the disease.
Sievers
Caroline
C
Center for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, Germany.
Platt
Nick
N
Perry
V Hugh
VH
Coleman
Michael P
MP
Conforti
Laura
L
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D019771:Axotomy; D018929:Cell Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000473:pathology / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D009994:Osmolar Concentration; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014855:Wallerian Degeneration / Q000378:metabolism / Q000473:pathology*
D017304:Annexin A5; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D019311:Staurosporine