Impact of opiate-HIV-1 interactions on neurotoxic signaling

Kurt F. Hauser, Nazira El-Hage, Shreya Buch, Avindra Nath, William R. Tyor, Annadora J. Bruce-Keller, Pamela E. Knapp

Research output: Contribution to journalReview articlepeer-review

Abstract

Opiate drug abuse exacerbates the pathogenesis of human immunodeficiency virus-1 (HIV-1) in the central nervous system through direct actions on glia and neurons. Opiate abuse causes widespread disruption of astroglial and microglial function, and significant increases in astroglial-derived proinflammatory cytokines and chemokines, which likely contributes to neuronal dysfunction, death, and HIV encephalitis. Neurons are also directly affected by opiate-HIV-1 interactions. HIV-1 and the viral proteins gp120 and Tat activate multiple caspase-dependent and caspase-independent proapoptotic pathways in neurons involving phosphatidylinositol 3-kinase (PI3 kinase)/Akt, as well as p38, c-Jun N-terminal kinase (JNK) and/or other mitogen-activated protein kinases (MAPKs). Opiates appear to decrease the threshold for HIV-1-mediated neurotoxicity by sending convergent signals that exacerbate proapoptotic events induced by viral and cellular toxic products. The synergistic proinflammatory and neurotoxic effects of opiate drugs on glia and neurons are largely mediated through μ opioid receptors, which are expressed by subpopulations of astroglia, microglia, and neurons. Opiate abuse intrinsically modifies the host response to HIV-1. Identification of how this occurs is providing considerable insight toward understanding the mechanisms underlying HIV-1-associated dementia.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalJournal of Neuroimmune Pharmacology
Volume1
Issue number1
DOIs
StatePublished - Mar 1 2006

Keywords

  • AIDS
  • Apoptosis
  • Astroglia
  • Caspase-3
  • Microglia
  • Monocyte chemoattractant protein-1 (MCP-1/CCL2)
  • Neuroimmunology
  • Neurons
  • c-Jun N-terminal kinase (JNK)
  • p38 mitogen-activated protein kinase (MAPK)
  • μ-opioid receptors

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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