Systemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid content of mouse cerebral cortex

Abstract

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.