The protective role of nitric oxide in a neurotoxicant-induced demyelinating model.
Demyelination is often associated with acute inflammatory events involving the recruitment-activation of microglia/macrophage, astrocytes, and leukocytes. The ultimate role of inflammatory products in demyelinating disease and in the survival of oligodendrocytes, the myelin forming cells, is unresolved. The current study examines the role of inducible NO synthase (iNOS)-derived NO in a neurotoxicant-induced model of demyelination. NO levels were greatly elevated in the midline corpus callosum during demyelination in genetically intact C57BL/6 mice, and this NO was due solely to the induction of iNOS, as the correlates of NO were not found in mice lacking iNOS. C57BL/6 mice lacking iNOS exhibited more demyelination, but did not display an increased overall cellularity in the corpus callosum, attributable to an unimpeded microglia/macrophage presence. An enhanced course of pathology was noted in mice lacking iNOS. This was associated with a greater depletion of mature oligodendrocytes, most likely due to apoptosis of oligodendrocytes. Microglia and astrocytes did not undergo apoptosis during treatment. Our results suggest a moderately protective role for NO during acute inflammation-association demyelination.
Arnett
Heather A
HA
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Hellendall
Ron P
RP
Matsushima
Glenn K
GK
Suzuki
Kinuko
K
Laubach
Victor E
VE
Sherman
Paula
P
Ting
Jenny P-Y
JP
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009836:Oligodendroglia / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D018696:Neuroprotective Agents; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D003471:Cuprizone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse