Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord.
In order to investigate the remyelinating potential of mature oligodendrocytes in vivo, we have developed a model of demyelination in the adult rat spinal cord in which some oligodendrocytes survive demyelination. A single intraspinal injection of complement proteins plus antibodies to galactocerebroside (the major myelin sphingolipid) resulted in demyelination followed by oligodendrocyte remyelination. Remyelination was absent when the spinal cord was exposed to 40 Grays of x-irradiation prior to demyelination, a procedure that kills dividing cells. Quantitative Rip immunohistochemical analysis revealed a similar density of surviving oligodendrocytes in x-irradiated and nonirradiated lesions 3 days after demyelination. Rip and bromodeoxyuridine double immunohistochemical analysis of demyelinated lesions indicated that Rip+ oligodendrocytes did not divide as an acute response to demyelination. Oligodendrocytes were also identified by Rip immunostaining and electron microscopy at late time points (3 weeks) within x-irradiated areas of demyelination. These oligodendrocytes extended processes that engaged axons, and on occasion formed myelin membranes, but did not lay down new myelin sheaths. These studies demonstrate that (a) oligodendrocytes that survive within a region of demyelination are not induced to divide in the presence of demyelinated axons, and (b) fully-differentiated oligodendrocytes are therefore postmitotic and do not contribute to remyelination in the adult CNS.
Keirstead
H S
HS
MRC Cambridge Centre for Brain Repair and Department of Clinical Veterinary Medicine, University of Cambridge, UK.
Blakemore
W F
WF
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008938:Mitosis / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology*; D014965:X-Rays
D000906:Antibodies; D005699:Galactosylceramides; C002454:galactocerebroside; D003165:Complement System Proteins