Cyclooxygenase 2 mRNA expression in rat brain after peripheral injection of lipopolysaccharide.
Inducible cyclooxygenase 2 (COX 2) converts arachidonic acid to prostaglandins, which are thought to mediate various peripheral lipopolysaccharide (LPS)-induced central effects, including generation of fever and activation of the hypothalamic-pituitary-adrenal axis. To localize prostaglandin production in the brain following peripheral LPS administration, COX 2 mRNA expression was examined by in situ hybridization histochemistry in rats injected intraperitoneally (i.p.) or intravenously (i.v.) with various doses of LPS or saline. Constitutive expression of COX 2 mRNA was found in neurons of cortex, hippocampus, and amygdala, but not in cells of the blood vessels. COX 2 mRNA levels were not altered in saline-injected animals as compared to non-injected controls. In LPS-injected animals, no consistent changes of neuronal COX 2 mRNA expression were observed. COX 2 mRNA expression appeared ex novo at 0.5-h post-injection in cells closely associated with blood vessels, however, ex novo labeling of the number of labeled cells increased to a peak at 2 h and subsided gradually to basal levels by 24 h. Initially, labeling was observed in cells comprising major surface-lying blood vessels and meninges. Later, vascular and perivascular cells associated with smaller penetrating blood vessels were labeled. This pattern of COX 2 mRNA induction is independent of the route and dose of the LPS injection. The induced COX 2 mRNA producing cells are identified as endothelial and leptomeningeal cells. Changes in COX 2 mRNA expression were not observed in circumventricular organs. These results suggest that peripheral LPS induces a rapid increase in COX 2 production throughout the vasculatures of the brain, which could affect the neuronal activity of widespread brain regions by elevating the levels of prostaglandins.
Quan
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Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892-4070, USA.
Whiteside
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M
Herkenham
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M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051546:Cyclooxygenase 2; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases