Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats (Retracted article. See vol.35, pg. 1386, 2015)
Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats (Retracted article. See vol.35, pg. 1386, 2015)
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DOI：
10.1038/jcbfm.2010.111
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发表时间：
2011-02-01
影响因子：
6.3
通讯作者：
Rapoport, Stanley I.
中科院分区：
文献类型：
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作者：
Basselin, Mireille;Ramadan, Epolia;Rapoport, Stanley I.
人类免疫缺陷病毒（HIV）相关感染涉及携带病毒的单核细胞进入大脑，随后是小胶质细胞活化、神经炎症和花生四烯酸（AA）代谢上调。HIV-1转基因（Tg）大鼠是一种非感染性HIV-1模型，在5个月大后表现出神经和行为异常。我们假设，大脑AA代谢将在体内老年HIV-1转基因大鼠升高。在[1-C-14] AA输注后，使用定量放射自显影术对未麻醉的7至9月龄大鼠的花生四烯酸从血浆掺入脑中进行成像。测定脑磷脂酶（PLA（2））活性和类花生酸浓度，并通过免疫染色定位酶。在HIV-1 Tg大鼠的81个脑区中，69个脑区的AA掺入系数k* 和AA代谢率J（in）显著高于对照大鼠，细胞溶质（c）PLA（2）-IV、分泌（s）PLA（2）和钙非依赖性（i）PLA（2）-VI的活性以及前列腺素E-2和白三烯B-4的浓度也显著高于对照大鼠。躯体感觉皮质的免疫染色显示神经元中cPLA（2）-IV、sPLA（2）-IIA和环氧合酶-2升高。在HIV-1 Tg大鼠中，脑AA掺入和AA代谢的其他标志物上调，其中已报道了神经系统变化和神经炎症。正电子发射断层扫描与[1-C-11] AA可用于测试是否脑AA代谢上调HIV-1感染患者，与认知和行为障碍。Journal of Cerebral Blood Flow & Metabolism（2011）31，486-493; doi：10.1038/jcbfm.2010.111; 2010年7月28日在线发表
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