title: Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation.
abstract: Neuroinflammation, caused by a 6-day intracerebroventricular infusion of lipopolysaccharide (LPS) in rats, is associated with the up-regulation of brain arachidonic acid (AA) metabolism markers. Because chronic LiCl down-regulates markers of brain AA metabolism, we hypothesized that it would attenuate increments of these markers in LPS-infused rats. Incorporation coefficients k* of AA from plasma into brain, and other brain AA metabolic markers, were measured in rats that had been fed a LiCl or control diet for 6 weeks, and subjected in the last 6 days on the diet to intracerebroventricular infusion of artificial CSF or of LPS. In rats on the control diet, LPS compared with CSF infusion increased k* significantly in 28 regions, whereas the LiCl diet prevented k* increments in 18 of these regions. LiCl in CSF infused rats increased k* in 14 regions, largely belonging to auditory and visual systems. Brain cytoplasmic phospholipase A(2) activity, and prostaglandin E(2) and thromboxane B(2) concentrations, were increased significantly by LPS infusion in rats fed the control but not the LiCl diet. Chronic LiCl administration attenuates LPS-induced up-regulation of a number of brain AA metabolism markers. To the extent that this up-regulation has neuropathological consequences, lithium might be considered for treating human brain diseases accompanied by neuroinflammation.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda 20892-0947, Maryland, USA. mirvasln@mail.nih.gov
authors.forename: Mireille
authors.initials: M
authors.lastname: Basselin
authors.forename: Nelly E
authors.initials: NE
authors.lastname: Villacreses
authors.forename: Ho-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jane M
authors.initials: JM
authors.lastname: Bell
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018692:Antimanic Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013929:Thromboxane B2 / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D018692:Antimanic Agents; D015415:Biomarkers; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D013929:Thromboxane B2; D010741:Phospholipases A; D018021:Lithium Chloride; D015232:Dinoprostone