Disturbed brain arachidonic acid metabolism in HIV‐1 transgenic rats

Abstract

Human immunodeficiency virus (HIV) is associated with neuroinflammation and related neuropathological co-morbidities, such as HIV-associated dementia and psychosis, following viral entry into the brain. The entry of viral-bearing HIV monocytes into the brain is associated with microglial activation, neuroinflammation and increased arachidonic acid (AA) signalling (Basselin M et al., J Cereb Blood Flow Metab., 2010), which is elevated in pathological conditions of excitotoxicity and inflammation. We hypothesized that AA turnover due to metabolic loss (of AA) in the brain, would be elevated in HIV-transgenic rats (HIV-Tg), a non-infectious HIV-1 model associated with neuroinflammation and behavioural abnormalities after 5 months of age. Brian AA turnover and fatty acid concentrations were measured after [1-(14)C]AA infusion to 7–9 months old, unanesthetized rats. Brain AA turnover due to metabolic loss increased by ~2-fold, and concentrations decreased by 14–18% in ethanolamine glycerophospholipids, choline glycerophospholipids, phosphatidylinositol and phosphatidylserine of HIV-Tg rats relative to controls. The results suggest upregulated AA metabolism in HIV-Tg rats, in which behavioural abnormalities, neurologic changes and neuroinflammation have been reported. This work was supported by the National Institute on Aging Intramural Program. Grant Funding Source: Intramural Research Funding from the National Institute on Aging