Diazepam inhibits HIV-1 Tat-induced migration of human microglia

J. R. Lokensgard, S. Hu, C. C. Hegg, S. A. Thayer, G. Gekker, P. K. Peterson

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

During HIV-1 encephalitis, the chemotaxis-inducing activity of Tat may enhance the viral life cycle through recruitment of additional susceptible microglial cells to foci of infection. Benzodiazepines (BDZs) readily penetrate the blood-brain barrier and are known to possess anti-inflammatory properties. Pretreatment of human microglial cells with peripheral (Ro5-4864) and mixed (diazepam), but not central (clonazepam), benzodiazepine receptor ligands was found to potently suppress HIV-1 Tat-induced chemotaxis. Application of Tat to microglial cells evokes an increase in intracellular calcium concentration ([Ca2+]i) that rapidly desensitizes the cells. Diazepam's inhibitory effect was associated with its ability to block Tat-induced [Ca2+]i mobilization. These data support the notion that through their effects on microglia, peripheral BDZ receptor ligands could alter the neuropathogenesis of HIV-1.

Original languageEnglish (US)
Pages (from-to)481-486
Number of pages6
JournalJournal of neurovirology
Volume7
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Diazepam
  • HIV-1
  • Microglia
  • Tat

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