Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats.
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)C]AA 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)PLA(2), and calcium independent (i)PLA(2)-VI, as well as prostaglandin E(2) and leukotriene B(4) 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)C]AA could be used to test whether brain AA metabolism is upregulated in HIV-1-infected patients, in relation to cognitive and behavioral disturbances.
Basselin
Mireille
M
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ramadan
Epolia
E
Igarashi
Miki
M
Chang
Lisa
L
Chen
Mei
M
Kraft
Andrew D
AD
Harry
G Jean
GJ
Rapoport
Stanley I
SI
D000465:Algorithms; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D001345:Autoradiography; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015497:HIV-1; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013929:Thromboxane B2 / Q000378:metabolism; D015854:Up-Regulation
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D015232:Dinoprostone