Cited by 52Fatty Acid Research and HealthInflammatory mediators and NSAID effectsEicosanoids and Hypertension Pharmacology

Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation

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Basselin, Mireille, Kim, Hyung-Wook, Chen, Mei, Ma, Kaizong, Rapoport, Stanley I., Murphy, Robert C., Farias, Santiago E.·2010·Journal of Lipid Research

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.

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  • The most commonly used therapeutic drugs-lithium and valproate-were able to reverse the inflammatory state in mood disorders.

    “Interestingly, the most commonly used therapeutic drugs—lithium and valproate—were able to reverse the inflammatory state in mood disorders [99–101].”

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Authors
Basselin, M., Kim, H.-W., Chen, M., Ma, K., Rapoport, S. I., Murphy, R. C., & Farias, S. E.
Affiliations
  • National Institutes of Health (US)
  • University of Colorado Denver (US)
Corresponding author
Basselin, Mireille
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2010-05
Volume
51
Issue
5
Pages
1049-1056
ISSN
0022-2275 (ISSN-L)
OpenAlex
W2093308618
Cited by
52
References
67
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 6 · 2012: 7
FWCI
5.81
Type
journal article
Language
en
Status
Retracted
Update notices
erratum (2018-08-01)
Open access
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (GM-069338)
  • National Institute on Aging
  • National Institute of General Medical Sciences (U54GM069338, GM 069338)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
lithium, neuroinflammation, lipopolysaccharide, arachidonic acid metabolism, docosahexaenoic acid, eicosanoids, docosanoids, prostaglandin E2, phospholipase A2, lipoxygenase, docosapentaenoic acid, intracerebroventricular infusion, brain lipid metabolism
MeSH terms
Animals, Anti-Inflammatory Agents, Bipolar Disorder, Body Weight, Brain, Catheterization, Dietary Fats, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Esterification, Inflammation, Lipopolysaccharides, Lithium, Male, Microwaves, Time Factors, Arachidonic Acid, Rats

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