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.