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Chronic Lithium Feeding Reduces Upregulated Brain Arachidonic Acid Metabolism in HIV-1 Transgenic Rat

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Abstract

HIV-1 transgenic (Tg) rats, a model for human HIV-1 associated neurocognitive disorder (HAND), show upregulated markers of brain arachidonic acid (AA) metabolism with neuroinflammation after 7 months of age. Since lithium decreases AA metabolism in a rat lipopolysaccharide model of neuroinflammation, and may be useful in HAND, we hypothesized that lithium would dampen upregulated brain AA metabolism in HIV-1 Tg rats. Regional brain AA incorporation coefficients k* and rates J in , markers of AA signaling and metabolism, were measured in 81 brain regions using quantitative autoradiography, after intravenous [1-14 C]AA infusion in unanesthetized 10-month-old HIV-1 Tg and age-matched wildtype rats that had been fed a control or LiCl diet for 6 weeks. k* and J in for AA were significantly higher in HIV-1 Tg than wildtype rats fed the control diet. Lithium feeding reduced plasma unesterified AA concentration in both groups and J in in wildtype rats, and blocked increments in k* (19 of 54 regions) and J in (77 of 81 regions) in HIV-1 Tg rats. These in vivo neuroimaging data indicate that lithium treatment dampened upregulated brain AA metabolism in HIV-1 Tg rats. Lithium may improve cognitive dysfunction and be neuroprotective in HIV-1 patients with HAND through a comparable effect.

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Acknowledgements

The research was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. No author has a financial or other conflict of interest related to this work.

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  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, Rm. 1S126 MSC 0947, Bethesda, MD, 20892, USA

    Epolia Ramadan, Mireille Basselin, Lisa Chang, Mei Chen, Kaizong Ma & Stanley I. Rapoport

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  1. Epolia Ramadan
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  2. Mireille Basselin
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Correspondence to Mireille Basselin.

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Ramadan, E., Basselin, M., Chang, L. et al. Chronic Lithium Feeding Reduces Upregulated Brain Arachidonic Acid Metabolism in HIV-1 Transgenic Rat. J Neuroimmune Pharmacol 7, 701–713 (2012). https://doi.org/10.1007/s11481-012-9381-0

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