Preferential vulnerability of astroglia and glial precursors to combined opioid and HIV-1 Tat exposure in vitro

Valeriya K. Khurdayan, Shreya Buch, Nazira El-Hage, Sarah E. Lutz, Susan M. Goebel, Indrapal N. Singh, Pamela E. Knapp, Jadwiga Turchan-Cholewo, Avindra Nath, Kurt F. Hauser

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus (HIV)-1 infection can cause characteristic neural defects such as progressive motor dysfunction, striatal pathology and gliosis. Recent evidence suggests that HIV-induced pathogenesis is exacerbated by heroin abuse and that the synergistic neurotoxicity is a direct effect of heroin on the CNS, an alarming observation considering the high incidence of HIV infection with injection drug abuse. Although HIV infection results in neurodegeneration, neurons themselves are not directly infected. Instead, HIV affects microglia and astroglia, which subsequently contributes to the neu rodegenerative changes. Opioid receptors are widely expressed by macroglia and macroglial precursors, and the activation of μ-opioid receptors can modulate programmed cell death, as well as the response of neural cells to cytotoxic insults. For this reason, we questioned whether opioid drugs might modify the vulnerability of macroglia and macroglial precursors to HIV-1 Tat protein. To address this problem, the effects of morphine and/or HIV Tat1-72 on the viability of macroglia and macroglial precursors were assessed in mixed-glial cultures derived from mouse striatum. Our findings indicate that sustained exposure to morphine and Tat1-72 viral protein induces the preferential death of glial precursors and some astrocytes. Moreover, the increased cell death is mediated by μ-opioid receptors and accompanied by the activation of caspase-3. Our results imply that opiates can enhance the cytotoxicity of HIV-1 Tat through direct actions on glial precursors and/or astroglia, suggesting novel cellular targets for HIV-opiate interactions.

Original languageEnglish (US)
Pages (from-to)3171-3182
Number of pages12
JournalEuropean Journal of Neuroscience
Volume19
Issue number12
DOIs
StatePublished - Jun 2004

Keywords

  • Drug abuse
  • Glial precursors
  • Human immunodeficiency virus
  • Morphine
  • Oligodendroglia
  • Opioid receptors
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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