HIV-1 tat and morphine have interactive effects on oligodendrocyte survival and morphology

Kurt F. Hauser, Yun Kyung Hahn, Valeriya V. Adjan, Shiping Zou, Shreya K. Buch, Avindra Nath, Annadora J. Bruce-Keller, Pamela E. Knapp

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus (HIV)-infected individuals who abuse opiates show faster progression to AIDS, and enhanced incidence of HIV-1 encephalitis. Most opiates with abuse liability are preferential agonists for l-opioid receptors (MORs), and MORs are expressed on both neurons and glia, including oligodendrocytes (OLs). Tat, gp120, and other viral toxins, cause neurotoxicity in vitro and/or when injected into brain, and co-exposure to opiates can augment HIV-1 protein-induced insults to both glial and neuronal populations. We examined the effects of HIV-1 Tat +/- opiate exposure on OL survival and differentiation. In vivo studies utilized transgenic mice expressing Tat1-86 regulated by an inducible glial fibrillary acidic protein promoter. Although MBP levels were unchanged on immunoblots, certain structural and apoptotic indices were abnormal. After only 2 days of Tat induction, OLs showed an upregulation of active caspase-3 that was enhanced by morphine exposure. Tat also upregulated TUNEL staining, but only in the presence of morphine. Tat significantly reduced the length of processes in Golgi-Kopsch impregnated OLs. A greater proportion of cells exhibited diminished or aberrant cytoplasmic processes, especially when mice expressing Tat were co-exposed to morphine. Collectively, our data show that OLs in situ are extremely sensitive to effects of Tat +/- morphine, although it is not clear if immature OLs as well as differentiated OLs are targeted equally. Significant elevations in caspase-3 activity and TUNEL labeling, and evidence of increased degeneration/regeneration of OLs exposed to Tat +/- morphine suggest that toxicity toward OLs may be accompanied by heightened OL turnover.

Original languageEnglish (US)
Pages (from-to)194-206
Number of pages13
JournalGlia
Volume57
Issue number2
DOIs
StatePublished - Jan 15 2009

Keywords

  • AIDS
  • Cell death
  • Drug abuse
  • Glial cell
  • Heroin
  • Myelin
  • NeuroAIDS
  • Opioid
  • Transgenic

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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