NEUROBIOLOGY OF AGING | 卷:33 |
HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits | |
Article | |
Hennig, Bernhard2  Toborek, Michal1  | |
[1] Univ Kentucky, Med Ctr, Mol Neurosci & Vasc Biol Lab, Dept Neurosurg, Lexington, KY 40536 USA | |
[2] Univ Kentucky, Coll Agr, Lexington, KY USA | |
关键词: HIV-1 infection; Amyloid; HIV-1; Aging; Blood-brain barrier; Tight junction proteins; Inflammation; | |
DOI : 10.1016/j.neurobiolaging.2011.06.004 | |
来源: Elsevier | |
【 摘 要 】
HIV-1-infected brains are characterized by elevated depositions of amyloid beta (A beta); however, the interactions between A beta 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 A beta 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 A beta and/or Tat. The present data indicate that increased brain levels of A beta can enhance vascular toxicity and proinflammatory responses induced by HIV-1 protein Tat. (C) 2012 Elsevier Inc. All rights reserved.
【 授权许可】
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