Apoptosis and proliferation of oligodendrocyte progenitor cells in the irradiated rodent spinal cord.
OBJECTIVE
Oligodendrocytes undergo early apoptosis after irradiation. The aim of this study was to determine the relationship between oligodendroglial apoptosis and proliferation of oligodendrocyte progenitor cells (OPC) in the irradiated central nervous system.


METHODS
Adult rats and p53 transgenic mice were given single doses of 2 Gy, 8 Gy, or 22 Gy to the cervical spinal cord. Apoptosis was assessed using TUNEL (Tdt-mediated dUTP terminal nick-end labeling) staining or by examining nuclear morphology. Oligodendrocyte progenitor cells were identified with an NG2 antibody or by in situ hybridization for platelet-derived growth factor receptor alpha. Proliferation of OPC was assessed by in vivo bromodeoxyuridine (BrdU) labeling and subsequent immunohistochemistry. Because radiation-induced apoptosis of oligodendroglial cells is p53 dependent, p53 transgenic mice were used to study the relationship between apoptosis and cell proliferation.


RESULTS
Oligodendrocyte progenitor cells underwent apoptosis within 24 h of irradiation in the rat. That did not result in a change in OPC density at 24 h. Oligodendrocyte progenitor cell density was significantly reduced by 2-4 weeks, but showed recovery by 6 weeks after irradiation. An increase in BrdU-labeled cells was observed at 2 weeks after 8 Gy or 22 Gy, and proliferating cells in the rat spinal cord were immunoreactive for NG2. The mouse spinal cord showed a similar early cell proliferation after irradiation. No difference was observed in the proliferation response in the spinal cord of p53 -/- mice compared with wild type animals.


CONCLUSIONS
Oligodendroglial cells undergo early apoptosis and OPC undergo early proliferation after ionizing radiation. However, apoptosis is not likely to be the trigger for early proliferation of OPC in the irradiated central nervous system.
Atkinson
Shelley L
SL
Discipline of Molecular and Cell Biology, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, ON, Canada.
Li
Yu-Qing
YQ
Wong
C Shun
CS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000502:physiology / Q000528:radiation effects*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000166:cytology / Q000528:radiation effects*; D013234:Stem Cells / Q000502:physiology / Q000528:radiation effects*