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 language | English (US) |
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Pages (from-to) | 194-206 |
Number of pages | 13 |
Journal | Glia |
Volume | 57 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2009 |
Externally published | Yes |
Keywords
- AIDS
- Cell death
- Drug abuse
- Glial cell
- Heroin
- Myelin
- NeuroAIDS
- Opioid
- Transgenic
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience