Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide.
In a rat model of acute neuroinflammation, produced by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide (LPS), we measured brain activities and protein levels of three phospholipases A2 (PLA2) and of cyclo-oxygenase-1 and -2, and quantified other aspects of brain phospholipid and fatty acid metabolism. The 6-day intracerebral ventricular infusion increased lectin-reactive microglia in the cerebral ventricles, pia mater, and the glial membrane of the cortex and resulted in morphological changes of glial fibrillary acidic protein (GFAP)-positive astrocytes in the cortical mantel and areas surrounding the cerebral ventricles. LPS infusion increased brain cytosolic and secretory PLA2 activities by 71% and 47%, respectively, as well as the brain concentrations of non-esterified linoleic and arachidonic acids, and of prostaglandins E2 and D2. LPS infusion also increased rates of incorporation and turnover of arachidonic acid in phosphatidylethanolamine, plasmenylethanolamine, phosphatidylcholine, and plasmenylcholine by 1.5- to 2.8-fold, without changing these rates in phosphatidylserine or phosphatidylinositol. These observations suggest that selective alterations in brain arachidonic acid metabolism involving cytosolic and secretory PLA2 contribute to early pathology in neuroinflammation.
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-1582, USA. plsetn@mail.nih.gov
Thad A
TA
Rosenberger
Nelly E
NE
Villacreses
Jonathan T
JT
Hovda
Francesca
F
Bosetti
Gayani
G
Weerasinghe
Robert N
RN
Wine
G Jean
GJ
Harry
Stanley I
SI
Rapoport
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008565:Membrane Proteins; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D015777:Eicosanoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010743:Phospholipids; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2