title: Astrogliopathy and oligodendrogliopathy are early events in CNS demyelination.
abstract: We examined the phenotypic composition of cells and the underlying mechanisms of demyelination following injection of lipopolysaccharide (LPS) into the corpus callosum of rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed fragmented DNA, which co-localized with oligodendrocytes in areas of demyelination following intracerebral injection with LPS. Immunostaining showed the presence of caspase 3 in cells which expressed the oligodendrocyte markers, suggesting activation of the apoptotic pathway. Commensurate reduction in glial fibrillary acid protein (GFAP)+/ gap junction protein connexin43+ (Cx43) cells, was also seen in the corpus callosum prior to histochemical evidence of demyelination. Expression of mRNA for proinflammatory cytokines was maximal 3 day postinjection, at a time when the numbers of TUNEL positive cells in the corpus callosum were declining and the total number of CD68+ cells peaked at day 14 postinjection. Our studies suggest that death of oligodendrocytes is an early event in LPS model of demyelination. We believe that the innate immune model of oligodendrocyte death will be useful in the development of neuroprotective agents capable of rescuing oligodendrocytes from apoptosis.
authors.affiliation: Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Zhang
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Yao
authors.forename: William O
authors.initials: WO
authors.lastname: Whetsell
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sriram
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides
keywords: apoptosis; astrocyte; demyelination; lipopolysaccharide; multiple sclerosis connexins; oligodendrocyte