| First Author | Chen L | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 8 | Pages | 1579-90 |
| PubMed ID | 21764480 | Mgi Jnum | J:188199 |
| Mgi Id | MGI:5439686 | Doi | 10.1016/j.neurobiolaging.2011.06.004 |
| Citation | Chen L, et al. (2012) HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits. Neurobiol Aging 33(8):1579-90 |
| abstractText | HIV-1-infected brains are characterized by elevated depositions of amyloid beta (Abeta); however, the interactions between Abeta and HIV-1 are poorly understood. In the present study, we administered specific HIV-1 protein Tat into the cerebral vasculature of 50-52-week-old double transgenic (B6C3-Tg) mice that express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) and are characterized by increased Abeta depositions in the brain. Exposure to Tat increased permeability across cerebral capillaries, enhanced disruption of zonula occludens (ZO)-1 tight junction protein, and elevated brain expression of matrix metalloproteinase-9 (MMP-9) in B6C3-Tg mice as compared with age-matched littermate controls. These changes were associated with increased leukocyte attachment and their transcapillary migration. The majority of Tat-induced effects were attenuated by treatment with a specific Rho inhibitor, hydroxyfasudil. The results of animal experiments were reproduced in cultured brain endothelial cells exposed to Abeta and/or Tat. The present data indicate that increased brain levels of Abeta can enhance vascular toxicity and proinflammatory responses induced by HIV-1 protein Tat. |
