Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.
We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs.
Chari
D M
DM
Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom. dmc35@cam.ac.uk
Huang
W L
WL
Blakemore
W F
WF
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity; D004996:Ethidium / Q000633:toxicity; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron / Q000295:instrumentation / Q000379:methods; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects / Q000648:ultrastructure; D011509:Proteoglycans / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D004791:Enzyme Inhibitors; D004996:Ethidium; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000099216:Chondroitin Sulfate Proteoglycan 4