Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 tat transgenic mice

Annadora J. Bruce-Keller, Jadwiga Turchan-Cholewo, Eric J. Smart, Theresa Geurin, Ashok Chauhan, Rollie Reid, Ruqiang Xu, Avindra Nath, Pamela E. Knapp, Kurt F. Hauser

Research output: Contribution to journalArticle

Abstract

HIV encephalitis (HIVE) is accompanied by brain inflamation, leukocyte infiltration, and glial activation, and HIV patients who abuse opiates are more likely to develop HIVE. To better understand how opiates could alter HIV-related brain inflammation, the expression of astrocyte (GFAP immunoreactivity) and macrophage/microglial (F4/80 or Mac1 immunoreactivity) markers in the striatum, and the percentage of 3-nitrotyrosine (3-NT) positive macrophages/microglia, was determined following a 2-day exposure to morphine (5 mg/kg/day via time-release, subcutaneous implant) and doxycycline in GFAP-driven, doxycycline-inducible HIV-1 Tat transgenic mice. Data show that both morphine and Tat induction via doxycycline increased astrocyte activation, with significant additive increases achieved with combined morphine and doxycycline exposure. By contrast, combined Tat induction and morphine exposure, but neither manipulation alone, significantly increased the proportion of macrophages/microglia present in the striatum of transgenic mice, although morphine exposure was necessary to elevate 3-NT codetection in Mac1-positive macrophages/microglia. Finally, Tat induction increased the percentage of neurons expressing active caspase-3, and this was even more significantly elevated by co-administration of morphine. In spite of elevations in caspase-3, neuronal TUNEL reactivity was unchanged in all groups, even after 10 days of Tat induction. Importantly, co-administration of naltrexone completely antagonized the effects of morphine. These findings indicate that morphine rapidly and significantly increases the activation of astrocytes and macrophages/microglia in the brains of inducible Tat transgenic mice, supporting the theory that early inflammatory changes in glia could underlie the development of HIVE in opiate-abusing AIDS patients.

Original languageEnglish (US)
Pages (from-to)1414-1427
Number of pages14
JournalGlia
Volume56
Issue number13
DOIs
StatePublished - Oct 2008

Keywords

  • Apoptosis
  • Caspase 3
  • HIV transgenic mouse model
  • Inflammation
  • Neuro-acquired immunodeficiency syndrome (neuroAIDS)
  • Opioid drug abuse
  • Oxidative stress
  • Reactive nitrogen products

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Bruce-Keller, A. J., Turchan-Cholewo, J., Smart, E. J., Geurin, T., Chauhan, A., Reid, R., Xu, R., Nath, A., Knapp, P. E., & Hauser, K. F. (2008). Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 tat transgenic mice. Glia, 56(13), 1414-1427. https://doi.org/10.1002/glia.20708