| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3069742 | Neurobiology of Disease | 2011 | 8 Pages |
Recent evidence suggests that cyclooxygenases COX1 and COX2 differentially affect brain immunity. Limited data exist about their expressional changes in neurodegenerative diseases such as neuro-AIDS. Here, we analyzed the regulation of non-neuronal COX1/2 expression in rhesus macaque brain during infection with SIVδ670 and antiretroviral treatment. COX1 was constitutively expressed in microglia and endothelial cells and was not changed in early SIV infection. Late stage of disease was characterized by increased COX1 expression in globally activated microglia, macrophage nodules, infiltrates, and multinucleated giant cells. Endothelial COX1 expression was unaltered. In contrast, COX2 was not expressed in non-neuronal cells in the brain of uninfected and asymptomatically SIV-infected monkeys but was induced in nodule- and syncytium-forming macrophages and in endothelial cells in areas with infiltrates and SIV in monkeys with AIDS. Antiretroviral treatment of AIDS-diseased monkeys with 6-chloro-2′,3′-dideoxyguanosine markedly reduced SIV burden, appearance of COX1-positive macrophage nodules, giant cells, and infiltrates, and COX2 induction in the brain. However, the number of COX1-positive diffuse microglia was still increased in antiretrovirally treated animals as compared to uninfected or asymptomatic SIV-infected monkeys. Our data imply that both COX isoforms are differentially regulated and may distinctly modulate local immune responses in the brain during lentiviral disease.
Research Highlights► COX1, and not COX2, is constitutively expressed in microglial and endothelial cells in rhesus monkey brain. ► COX1 is globally upregulated in microglia/macrophages during SIV-induced encephalitis in monkeys with AIDS. ► COX2 is focally induced in a subset of microglia/macrophages and endothelial cells in areas of viral burden in SIV encephalitis. ► Antiretroviral treatment with lipophilic 6-Cl-ddG reverses focal COX2 reactions and viral burden but not global microglial COX1 reaction in AIDS-diseased monkey brain.
