Systemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid content of mouse cerebral cortex.
Systemic infections and injection of endotoxin are known to increase L-tryptophan release from skeletal muscle and increase systemic L-tryptophan catabolism through the kynurenine pathway. To investigate the effects of systemically administered endotoxin on brain L-tryptophan metabolites. C57BL6/6NCR mice were given an intraperitoneal injection of 10 micrograms of lipopolysaccharide from Salmonella abortus equii and samples of serum and cerebral cortex collected. After 9 h, serum L-tryptophan concentration was decreased by 51%. At 9 h and 24 h, increases in L-tryptophan metabolites in cerebral cortex were: L-tryptophan, 42% and 39%; 5-hydroxyindoleacetic acid, 38% and 67%; 3-hydroxykynurenine, 235% and 381%; and quinolinic acid, 76% and 306%. Cortical quinolinic acid concentration was still elevated at 48 h (88%) and 72 h (79%) after lipopolysaccharide. No significant changes in cortical serotonin concentrations were found at the time points examined. When L-tryptophan (0.37 mmol/kg) was administered systemically to either normal or lipopolysaccharide-treated mice, increases in cortical L-tryptophan, serotonin, 5-hydroxyindoleacetic acid and 3-hydroxykynurenine concentrations were largest in mice treated with both lipopolysaccharide and L-tryptophan. These results suggest that disturbances in L-tryptophan metabolism that follow systemic endotoxin administration extend to the central nervous system. The consequences of these changes in L-tryptophan metabolites remain to be determined.
Heyes
M P
MP
Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892.
Quearry
B J
BJ
Markey
S P
SP
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D012475:Salmonella; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism*
D004731:Endotoxins; D011725:Pyridines; D011805:Quinolinic Acids; C005045:3-hydroxykynurenine; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D017378:Quinolinic Acid