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Effect of Age on Variables Influencing the Supply of Tryptophan to the Brain


Address correspondence and reprint requests to G. Sarna, Department of Neurochemistry, 33 John's Mews, London WC1N 2NS, U.K.


Abstract: The relations of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentrations of tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the forebrain were investigated in rats of different ages (from 8 days to 16 months after birth). In brain, tryptophan fell by 46%, whereas 5-HT rose by 20% between 8 and 40/42 days after birth. Thereafter, the levels of both tryptophan and 5-HT remained essentially constant. Brain 5-HIAA showed a more complex pattern, rising by 63% between 8 and 19 days, falling between 19 and 40/42 days, and then gradually rising until values at 16 months were significantly higher than those at 40/42 days. In plasma, the concentrations of free fatty acids, free and total tryptophan, and large neutral amino acids all decreased between 8 and 19 days and thereafter either remained constant or increased slowly, the exception being total tryptophan values, which showed large increases between 28/30 and 60/70 days. Also, the unidirectional uptake of tryptophan from blood to brain was determined using a carotid artery injection technique. Uptake values obtained using a tracer concentration of tryptophan in the injection solution decreased progressively with age. Kinetic analysis of the data in terms of the Michaelis-Menten equation for carrier-mediated transport indicated significantly lower values for Vmax and KD (a component for nonsaturable transport) in 6-month-old rats as compared to 19-day-old suckling rats, whereas Km values were the same at both ages. Detailed analysis of these results indicated that the age-related changes in brain tryptophan were largely explicable in terms of plasma free tryptophan in association with blood-brain transport characteristics; moderate differences in concentration of amino acids competing for transport were without apparent effect between 19 days and 16 months. The larger differences between 8 and 19 days after birth could be important.