HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits

Lei Chen, Jeong June Choi, Yean Jung Choi, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

HIV-1-infected brains are characterized by elevated depositions of amyloid beta (Aβ); however, the interactions between Aβ 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 Aβ 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 Aβ and/or Tat. The present data indicate that increased brain levels of Aβ can enhance vascular toxicity and proinflammatory responses induced by HIV-1 protein Tat.

Original languageEnglish (US)
Pages (from-to)1579-1590
Number of pages12
JournalNeurobiology of aging
Volume33
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Aging
  • Amyloid
  • Blood-brain barrier
  • HIV-1
  • HIV-1 infection
  • Inflammation
  • Tight junction proteins

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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