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Dendritic pathology and neuronal injury induced by Tat and opiates in a transgenic model of HIV‐1 encephalitis
Author(s) -
Hauser Kurt F,
Buch Shreya K,
ElHage Nazira,
TurchenCholewo Jadwiga,
BruceKeller Annadora J,
Nath Avindra,
Knapp Pamela E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.717.1
Subject(s) - glial fibrillary acidic protein , microglia , dendritic spine , morphine , proinflammatory cytokine , naltrexone , pharmacology , (+) naloxone , chemistry , medicine , opioid , endocrinology , inflammation , immunohistochemistry , hippocampal formation , receptor
To assess the mechanisms by which opiate abuse exacerbates HIV‐1 encephalitis (HIVE), morphine (5 mg/day) and/or naltrexone (6 mg/day) were administered via s.c. implant to wild type or transgenic (tg) mice expressing Tat 1–86 regulated by a doxycycline‐inducible glial fibrillary acidic protein (GFAP) promoter. Tat induction or morphine exposure significantly increased the proportion of cleaved caspase−3 immunoreactive, but not TUNEL reactive, striatal neurons at 2 d. Despite increases in caspase−3 detection, neuron numbers appeared stable at 2 and 7 d. Instead, Tat induction or morphine exposure caused marked reductions in dendritic length and spine density (Golgi‐impregnated medium spiny neurons) at 7 d. When total spine losses are considered, combined Tat induction and morphine caused additive reductions in dendritic complexity. Neuronal injury was accompanied by significant increases in glial activation (assessed by increased GFAP and F4/80 immunoreactive astrocytes and macrophages/microglia, respectively) and proinflammatory chemokines (RANTES and MCP‐1). The effects of morphine were prevented by naltrexone. Our findings suggest that HIV‐1 Tat and chronic opiates contribute to the neurocognitive defects in neuroAIDS through interactive, non‐lethal reductions in dendritic length and spine density. Support: DA19398, DA18633.