title: [Chronological analyses of neuropathological and molecular biological changes in affected spinal cord of HTLV-I-infected rat (HAM rat disease)].
abstract: The author chronologically analyzed neuropathological aspects of the demyelination process in spinal cords of a rat model of human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from early asymptomatic to late disease stage for clarifying the pathogenetic roles of HTLV-I in central nervous system. There was no significant difference in histopathological and immunohistochemical findings between the rats within 7 months after the HTLV-I infection and age-matched controls. The first sign of demyelination was the appearance of apoptotic cell death beginning at 7 months after the infection and the apoptotic cell number gradually increased to 12 cells per a whole horizontal section of the spinal cord, in contrast to 5 cells in the control rats. The majority of the apoptotic cells were shown to be oligodendrocytes by immunohistochemical stain with an anti-myelin oligodendrocyte glycoprotein antibody. Increment of activated microglia/macrophages started at 9 months after the infection and they rapidly increased from 15 months to reach 600 cells per a whole horizontal section, in contrast to 300 cells in the control rats. Rapid increase of gemistocytic astrocytes was found from 20 months after the infection (the late disease stage). Molecular analysis of the spinal cords revealed that HTLV-I provirus DNA was evident as early as 4 months after the infection, and massages of HTLV-I pX and tumor necrosis factor (TNF)-alpha began to be expressed at 7 months, just before or at the same time as the appearance of the apoptotic cells. The collective evidence suggests that the apoptotic death of oligodendrocytes, which may be induced either directly by the local expression of HTLV-I or indirectly by upregulated cytotoxic humoral mediators, such as TNF-alpha, through the transactive function of p40 Tax, is the major cause of chronic progressive myelopathy in WKAH rats with HTLV-I infection.
authors.affiliation: First Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Ohya
mesh_terms: D000818:Animals; D017209:Apoptosis; D003711:Demyelinating Diseases / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D008297:Male; D009836:Oligodendroglia / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000473:pathology* / Q000821:virology; D011533:Proviruses / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000821:virology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha