Kynurenic acid is present in the rat brain and its content increases during development and aging processes

The content of kynurenic acid, a tryptophan (TRP) metabolite which acts as an antagonist of the excitatory amino acid receptors, was measured in the brain, blood, liver and kidney of rats of different ages, using a sensitive and specific method based on ion exchange chromatography and high-performance liquid chromatography (HPLC). In a portion of the cortex of these animals the content of serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) and of TRP was also measured using HPLC and electrochemical detection. The brain content of kynurenic acid was extremely low during the first week of life measuring 15 +/- 3 pmol/g protein (mean +/- S.E.M.), was found to be 320 +/- 31 at 3 months and continued to increase reaching levels of 747 +/- 116 at 18 months of age. Aging failed to change kynurenate content in the liver and kidney while blood kynurenate concentration increased from 28 +/- 5 (pmol/ml) in 3 months old rats to 65 +/- 10 in those 18 months old. The accumulation of kynurenate in the brain was not due to an increased availability of TRP to the central nervous system of aged rats. In fact, the cortical content of this amino acid was slightly lower in animals 18 months old than in those 3 months old. These large changes of the brain content of an electrophysiologically active TRP metabolite such as kynurenic acid could help explain the functional differences present in the brain of newborn and aged animals.