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)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.

• Authors: Mireille Basselin, Epolia Ramadan, Miki Igarashi, Lisa Chang, Mei Chen, Andrew D Kraft, G Jean Harry, Stanley I Rapoport
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 31 Issue 2 Pg. 486-93 (Feb 2011) ISSN: 1559-7016 [Electronic] United States
• PMID: 20664612 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Retracted Publication)

Chemical References

• Fatty Acids
• Fatty Acids, Nonesterified
• Leukotriene B4
• Docosahexaenoic Acids
• Arachidonic Acid
• Thromboxane B2
• Cyclooxygenase 2
• Phospholipases A2
• Dinoprostone

Topics

• Algorithms
• Animals
• Arachidonic Acid (biosynthesis)
• Autoradiography
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Docosahexaenoic Acids (metabolism)
• Fatty Acids (metabolism)
• Fatty Acids, Nonesterified (blood)
• HIV-1
• Humans
• Immunohistochemistry
• Kinetics
• Leukotriene B4 (metabolism)
• Male
• Phospholipases A2 (metabolism)
• Rats
• Rats, Inbred F344
• Rats, Sprague-Dawley
• Rats, Transgenic
• Thromboxane B2 (metabolism)
• Up-Regulation