Reactive microglia in dysmyelination and demyelination.
The relationship between microglial activation and dysmyelination/demyelination was analyzed in a long-lived myelin mutant, the Long Evans shaker (les) rat, which exhibits early dysmyelination and a later loss of abnormal myelin sheaths. A microglial reaction characterized by progressive morphological transformation and increasing cell density was localized exclusively to white matter during postnatal 2-4 weeks, suggesting a microglial response to dysmyelination and oligodendroglial pathology. A further microglial reaction as marked by microglial expression of MHC II and a concomitant expression in the brain and spinal cord of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) began around 4 weeks when the remaining myelin was lost. Ultrastructurally, activated microglia ingested numerous myelin figures, suggestive of active phagocytosis. Thus, this study indicates that microglial reaction is graded in chronic neurological disorders and suggests that MHC II expression marks a functional change of activated microglia.
Zhang
S C
SC
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706-1102, USA. zhangs@svm.vetmed.wisc.edu
Goetz
B D
BD
Carré
J L
JL
Duncan
I D
ID
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D048429:Cell Size; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology*; D015870:Gene Expression / Q000502:physiology; D005911:Gliosis / Q000276:immunology / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009836:Oligodendroglia / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains; D013116:Spinal Cord / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat