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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Human immunodeficiency virus-1 protein tat and methamphetamine interactions
Shaji Theodore1, Stephanie Stolberg, Wayne A Cass
1Department of Neurology, University of Kentucky, 260 Health Science Research Building, 1095 V.A. Drive, Lexington, KY 40536-0305, USA.
Annals of the New York Academy of Sciences
|November 16, 2006
Summary
Human immunodeficiency virus-1 (HIV-1) and methamphetamine (METH) synergistically damage brain dopamine terminals. This neurotoxicity involves Tumor Necrosis Factor-alpha but not directly glial cell activation.
Area of Science:
- Neuroscience
- Toxicology
- Infectious Diseases
Background:
- Human immunodeficiency virus-1 (HIV-1) impacts the central nervous system (CNS), particularly basal ganglia structures.
- Methamphetamine (METH) abuse, common in HIV-1 patients, also targets basal ganglia and dopaminergic terminals.
- Previous work showed synergistic loss of striatal dopamine and DAT binding with coexposure to HIV-1 Tat protein and METH.
Purpose of the Study:
- To confirm dopamine terminal degeneration as the cause of synergistic dopamine loss.
- To investigate the role of glial activation in this neurotoxicity.
- To explore the involvement of TNF-alpha in the synergistic mechanism.
Main Methods:
- Silver staining and tyrosine hydroxylase (TH) immunohistochemistry to assess dopamine terminal integrity.
- Glial fibrillary acidic protein (GFAP) and OX-42 staining for astrocyte and microglia activation.
- Investigation of the cytokine TNF-alpha's role in the synergistic neurotoxicity.
Main Results:
- Synergistic loss of dopamine is confirmed to result from dopamine terminal degeneration.
- The observed neurotoxicity is not directly correlated with the number of activated glial cells.
- Tumor Necrosis Factor-alpha (TNF-alpha) is implicated in the synergistic neurotoxicity of Tat and METH.
Conclusions:
- HIV-1 Tat protein and METH synergistically induce dopamine terminal degeneration in the striatum.
- Glial activation is not the primary driver of this neurotoxicity, though it is present.
- TNF-alpha plays a significant role in mediating the combined neurotoxic effects of HIV-1 Tat and METH.
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