| Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats. | |
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MedLine Citation:
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PMID: 20664612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mireille Basselin; Epolia Ramadan; Miki Igarashi; Lisa Chang; Mei Chen; Andrew D Kraft; G Jean Harry; Stanley I Rapoport |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-07-28 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-04 Completed Date: 2011-03-17 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 486-93 Citation Subset: IM |
Affiliation:
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Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Grant Support | |
ID/Acronym/Agency:
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Z01 AG000151-01/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Fatty Acids, Nonesterified; 25167-62-8/Docosahexaenoic Acids; 363-24-6/Dinoprostone; 506-32-1/Arachidonic Acid; 54397-85-2/Thromboxane B2; 71160-24-2/Leukotriene B4; EC 1.14.99.1/Cyclooxygenase 2; EC 3.1.1.4/Phospholipases A2 |
| Comments/Corrections | |
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