A rat model for human T lymphocyte virus type I-associated myeloneuropathy. down-regulation of bcl-2 expression and increase in sensitivity to TNF-alpha of the spinal oligodendrocytes.
We reported that the tumor necrosis factor-alpha (TNF-alpha) expression and apoptotic death of oligodendrocytes appeared to be a major pathogenesis of the demyelination of spinal cords of Wistar-King-Aptekman-Hokudai (WKAH) rats with human T lymphocyte virus type I (HTLV-I) infection, HAM rats. In the present study, we examined the sensitivity to TNF-alpha-induced cell death of in vitro-separated oligodendrocytes from HTLV-I-infected WKAH rats. Although the number of non-viable oligodendrocytes increased by adding recombinant TNF-alpha, in a dose-dependent manner, in both HTLV-I-infected and uninfected control rats, oligodendrocytes from the infected rats were more susceptible to TNF-alpha. In situ detection of DNA fragmentation showed apoptotic death of oligodendrocytes. The expression of bcl-2, an anti-apoptotic gene, was strongly down-regulated in oligodendrocytes of the infected rats but not in the control rats. We suggest that the down-regulation of bcl-2 expression in the oligodendrocytes of the HTLV-I-infected rats may increase the susceptibility to TNF-alpha-induced apoptosis of oligodendrocytes, the result being development of HTLV-I-induced myeloneuropathy in rats.
Jiang
X
X
Department of Pathology, Hokkaido University School of Medicine, Kita-ku, Kita-15, Nishi-7, Sapporo, Japan.
Ikeda
H
H
Tomaru
U
U
Morita
K
K
Tanaka
Y
Y
Yoshiki
T
T
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D015536:Down-Regulation; D016356:Gene Products, tax / Q000378:metabolism; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015493:Paraparesis, Tropical Spastic / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D016356:Gene Products, tax; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha