| First Author | Iida R | Year | 2000 |
| Journal | FASEB J | Volume | 14 |
| Issue | 7 | Pages | 1023-31 |
| PubMed ID | 10783158 | Mgi Jnum | J:61804 |
| Mgi Id | MGI:1355606 | Doi | 10.1096/fasebj.14.7.1023 |
| Citation | Iida R, et al. (2000) Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-alpha gene. FASEB J 14(7):1023-31 |
| abstractText | Brain levels of TNF-alpha 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-alpha processing or its receptors has led us to investigate the role of TNF-alpha in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-alpha 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. TNF-alpha-(-/-) 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-alpha-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-alpha-(-/-) 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-alpha-(-/-) mice. While the loss of TNF-alpha 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-alpha-(-/-) mice. These findings directly support a role for TNF-alpha in the neurodegenerative processes associated with viral infections such as HIV-1. |
