期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 31, 期 2, 页码 486-493出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2010.111
关键词
arachidonic acid; brain imaging; eicosanoids; HIV-1; phospholipase A(2)
资金
- National Institute on Aging
- National Institute of Environmental Health Science, NIH
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-C-14] 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-C-11] AA could be used to test whether brain AA metabolism is upregulated in HIV-1-infected patients, in relation to cognitive and behavioral disturbances. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 486-493; doi: 10.1038/jcbfm.2010.111; published online 28 July 2010
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