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Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation.
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Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation.
J Lipid Res. 2010 May;51(5):1049-56. Epub 2009 Dec 29.
Lithium modifies brain arachidonic and docosahexaenoic metabolism in
rat lipopolysaccharide model of neuroinflammation.
Basselin M, Kim HW, Chen M, Ma K, Rapoport SI, Murphy RC, Farias SE.
Brain Physiology and Metabolism Section, National Institute on Aging,
National Institutes of Health, Bethesda, MD, USA.
mirva...@mail.nih.gov
Abstract
Neuroinflammation, caused by 6 days of intracerebroventricular
infusion of a low dose of lipopolysaccharide (LPS; 0.5 ng/h),
stimulates brain arachidonic acid (AA) metabolism in rats, but 6 weeks
of lithium pretreatment reduces this effect. To further understand
this action of lithium, we measured concentrations of eicosanoids and
docosanoids generated from AA and docosahexaenoic acid (DHA),
respectively, in high-energy microwaved rat brain using LC/MS/MS and
two doses of LPS. In rats fed a lithium-free diet, low (0.5 ng/h)- or
high (250 ng/h)-dose LPS compared with artificial cerebrospinal fluid
increased brain unesterified AA and prostaglandin E(2) concentrations
and activities of AA-selective Ca(2+)-dependent cytosolic
phospholipase A(2) (cPLA(2))-IV and Ca(2+)-dependent secretory
sPLA(2). LiCl feeding prevented these increments. Lithium had a
significant main effect by increasing brain concentrations of
lipoxygenase-derived AA metabolites, 5- hydroxyeicosatetraenoic acid
(HETE), 5-oxo-eicosatetranoic acid, and 17-hydroxy-DHA by 1.8-, 4.3-
and 1.9-fold compared with control diet. Lithium also increased 15-
HETE in high-dose LPS-infused rats. Ca(2+)-independent iPLA(2)-VI
activity and unesterified DHA and docosapentaenoic acid (22:5n-3)
concentrations were unaffected by LPS or lithium. This study
demonstrates, for the first time, that lithium can increase brain 17-
hydroxy-DHA formation, indicating a new and potentially important
therapeutic action of lithium.
PMID: 20040630 [PubMed - in process]PMCID: PMC2853431 [Available on
2011/5/1]
Lithium modifies brain arachidonic and docosahexaenoic metabolism in
rat lipopolysaccharide model of neuroinflammation.
Basselin M, Kim HW, Chen M, Ma K, Rapoport SI, Murphy RC, Farias SE.
Brain Physiology and Metabolism Section, National Institute on Aging,
National Institutes of Health, Bethesda, MD, USA.
mirva...@mail.nih.gov
Abstract
Neuroinflammation, caused by 6 days of intracerebroventricular
infusion of a low dose of lipopolysaccharide (LPS; 0.5 ng/h),
stimulates brain arachidonic acid (AA) metabolism in rats, but 6 weeks
of lithium pretreatment reduces this effect. To further understand
this action of lithium, we measured concentrations of eicosanoids and
docosanoids generated from AA and docosahexaenoic acid (DHA),
respectively, in high-energy microwaved rat brain using LC/MS/MS and
two doses of LPS. In rats fed a lithium-free diet, low (0.5 ng/h)- or
high (250 ng/h)-dose LPS compared with artificial cerebrospinal fluid
increased brain unesterified AA and prostaglandin E(2) concentrations
and activities of AA-selective Ca(2+)-dependent cytosolic
phospholipase A(2) (cPLA(2))-IV and Ca(2+)-dependent secretory
sPLA(2). LiCl feeding prevented these increments. Lithium had a
significant main effect by increasing brain concentrations of
lipoxygenase-derived AA metabolites, 5- hydroxyeicosatetraenoic acid
(HETE), 5-oxo-eicosatetranoic acid, and 17-hydroxy-DHA by 1.8-, 4.3-
and 1.9-fold compared with control diet. Lithium also increased 15-
HETE in high-dose LPS-infused rats. Ca(2+)-independent iPLA(2)-VI
activity and unesterified DHA and docosapentaenoic acid (22:5n-3)
concentrations were unaffected by LPS or lithium. This study
demonstrates, for the first time, that lithium can increase brain 17-
hydroxy-DHA formation, indicating a new and potentially important
therapeutic action of lithium.
PMID: 20040630 [PubMed - in process]PMCID: PMC2853431 [Available on
2011/5/1]
LittleFighter- Posts : 1114
Join date : 2009-07-07
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