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

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.

Indoleamines in the Hypothalamus and Area of the Midbrain Raphe Nuclei of Male and Female Rats throughout Postnatal Development

“…The pattern of changes in 5-HIAA content in the HPOA throughout postnatal development, with a maximum around day 20 (table I), agrees with previously reported patterns from 'forebrain' or whole brain [6,45]. However, the abrupt increase in the content of 5-HT in the HPOA between days 12 and 20 compared to the much more steady pattern in the M R (table I) was not reported in forebrain by Bourgoin et al [6] or in whole brain by Santa et al [45].…”

“…However, the abrupt increase in the content of 5-HT in the HPOA between days 12 and 20 compared to the much more steady pattern in the M R (table I) was not reported in forebrain by Bourgoin et al [6] or in whole brain by Santa et al [45]. In contrast to the raphe nuclei, maturation of 5-HT systems in the H PO A is not well advanced at birth and, in terms of innervation and terminal formation, extends throughout the first 3 postnatal weeks [35,36], The development of the 5-HT neuronal net work within the HPOA probably contributes to the increas ing 5-HT concentrations in the HPOA during the first 3 postnatal weeks (table I).…”

“…therefore, may have masked any changes in the M R by a dilution effect with other tissue. The marked changes in the concentrations of 5-HT in the H POA and to a lesser extent the MR and 5-HIAA in both areas seen throughout the first 3 postnatal weeks are probably the result of changes in plasma tryptophan metabolism [45,56], trypto phan hydroxylase activity [16,23,46], and monoamine oxi dase A activity [6,42] reported to occur during this period. However, a comparison of the data in table I throughout the first 3 weeks shows that the concentrations of each amine did not change to the same degree in each area which suggests that changes in plasma tryptophan metabolism and enzyme activities affect each area to different extents.…”

Phenylalanine Uptake in Neonatal and Infant Rat Brain

“…De velopmental changes in the blood-brain bar rier (BBB) might play a role here, since there is some evidence for changes with age in the cerebral influx rate of large neutral amino acids from physiological blood levels. Re sults obtained with the most frequently em ployed approach, the rapid intracarotid in jection technique of Oldendorf [8], showed that the brain uptake index (BUI) for trypto phan in rabbits decreases during the first 28 postnatal days [9], In rats, the BUI for tryp tophan was reported to be higher in the late suckling period than in adulthood [10]. Whether there is also a change early on is not known, since the 19th postnatal day was the youngest age at which the BUI of an amino acid (that of tryptophan and valine) has been determined in rats [10,11], Adaptation of the Oldendorf method [8] to younger rats was, therefore, one of our objectives.…”

“…Re sults obtained with the most frequently em ployed approach, the rapid intracarotid in jection technique of Oldendorf [8], showed that the brain uptake index (BUI) for trypto phan in rabbits decreases during the first 28 postnatal days [9], In rats, the BUI for tryp tophan was reported to be higher in the late suckling period than in adulthood [10]. Whether there is also a change early on is not known, since the 19th postnatal day was the youngest age at which the BUI of an amino acid (that of tryptophan and valine) has been determined in rats [10,11], Adaptation of the Oldendorf method [8] to younger rats was, therefore, one of our objectives. This paper presents results indicating that the BUI for Phe declines appreciably during the first 3 weeks of age, and discusses develop mental changes in the BBB which might con tribute to the coincident decrease of Phe accumulation in the brain of hyperphenylal aninémie animals.…”