The simian immunodeficiency virus (SIV) macaque model resembles human immunodeficiency virus-
acquired immunodeficiency syndrome (
AIDS) and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-
AIDS has been reported, but limited data exist for the
cholinergic system and
lipid mediators such as
prostaglandins. Here, we analyzed
cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting
enzymes for
prostaglandin synthesis,
cyclooxygenase isotypes 1 and 2 (COX1 and COX2) in the brains of SIV-infected macaques with or without
encephalitis and antiretroviral
therapy and uninfected controls.Cyclooxygenase isotype 1, but not COX2, was coexpressed with markers of
cholinergic phenotype, that is,
choline acetyltransferase and
vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human, brain.
Cyclooxygenase isotype 1 was decreased in basal forebrain neurons in macaques with
AIDS versus uninfected and asymptomatic SIV-infected macaques. The VAChT-positive fiber density was reduced in frontal, parietal, and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in
AIDS-diseased macaques that received
6-chloro-2',3'-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced
cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate
cholinergic basal forebrain neurons; it may be functionally important and a critical
biomarker of
cholinergic dysregulation accompanying lentiviral
encephalopathy. These results further imply that insufficiently prompt initiation of antiretroviral
therapy in lentiviral
infection may lead to neurostructurally unremarkable but neurochemically prominent irreversible brain damage.