Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.
Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by eight days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis.
Sun
Fang
F
Department of Neuroscience, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Lin
Chien-Liang Glenn
CL
McTigue
Dana
D
Shan
Xiu
X
Tovar
C Amy
CA
Bresnahan
Jacqueline C
JC
Beattie
Michael S
MS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001369:Axons / Q000473:pathology*; D019070:Cell Lineage / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D009836:Oligodendroglia / Q000166:cytology / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000502:physiology; D019051:Rhizotomy / Q000379:methods*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000601:surgery; D013234:Stem Cells / Q000166:cytology / Q000473:pathology*; D014855:Wallerian Degeneration / Q000473:pathology* / Q000517:prevention & control