Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene

Ryuichi Iida, Kuniaki Saito, Kiyofumi Yamada, Anthony S. Basile, Kenji Sekikawa, Masao Takemura, Hidehiko Fujii, Hisayasu Wada, Mitsuru Seishima, Toshitaka Nabeshima

研究成果: Article

32 引用 (Scopus)


Brain levels of TNF-α increase in many inflammatory conditions, including HIV-1 infection, and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-α processing or its receptors has led us to investigate the role of TNF-α in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-α gene. Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNFα-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-α-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-α-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5- infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-α-(-/-) mice. While the loss of TNF-α appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-α-(-/-) mice. These findings directly support a role for TNF-α in the neurodegenerative processes associated with viral infections such as HIV-1.

ジャーナルFASEB Journal
出版物ステータスPublished - 16-05-2000


All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


Iida, R., Saito, K., Yamada, K., Basile, A. S., Sekikawa, K., Takemura, M., Fujii, H., Wada, H., Seishima, M., & Nabeshima, T. (2000). Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-α gene. FASEB Journal, 14(7), 1023-1031.