Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats

Abstract

Human immunodeficiency virus (HIV)-associated infection involves the entry of virus-bearing monocytes into the brain, followed by microglial activation, neuroinflammation, and upregulated arachidonic acid (AA) metabolism. The HIV-1 transgenic (Tg) rat, a noninfectious HIV-1 model, shows neurologic and behavioral abnormalities after 5 months of age. We hypothesized that brain AA metabolism would be elevated in older HIV-1 Tg rats in vivo. Arachidonic acid incorporation from the plasma into the brain of unanesthetized 7-to-9-month-old rats was imaged using quantitative autoradiography, after 1- 14 CAA infusion. Brain phospholipase (PLA 2) activities and eicosanoid concentrations were measured, and enzymes were localized by immunostaining. AA incorporation coefficients k and rates J in, measures of AA metabolism, were significantly higher in 69 of 81 brain regions in HIV-1 Tg than in control rats, as were activities of cytosolic (c)PLA 2-IV, secretory (s)PLA2, and calcium independent (i)PLA 2-VI, as well as prostaglandin E2 and leukotriene B4 concentrations. Immunostaining of somatosensory cortex showed elevated cPLA 2-IV, sPLA 2-IIA, and cyclooxygenase-2 in neurons. Brain AA incorporation and other markers of AA metabolism are upregulated in HIV-1 Tg rats, in which neurologic changes and neuroinflammation have been reported. Positron emission tomography with 1- 11 CAA could be used to test whether brain AA metabolism is upregulated in HIV-1-infected patients, in relation to cognitive and behavioral disturbances. © 2011 ISCBFM All rights reserved.