Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids

Abstract

When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.We have shown that when plasma tryptophan concentrations rise in rats receiving low doses of tryptophan ( I ) or subconvulsive doses of insulin (2), or in rats consuming a carbohydrate diet (3), brain tryptophan and serotonin concentrations also increase. Such variations in amine concentration reflect the general dependence of the rate of serotonin formation on the degree of saturation of tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis ( 4 ) . We suggested that the brain tryptophan elevations were direct responses to the increases in plasma tryptophan, and that, generally, any perturbations which increased plasma tryptophan would similarly increase brain tryptophan and serotonin (3). Since dietary protein should elevate plasma tryptophan both by eliciting insulin secretion and by providing new tryptophan, we anticipated (3) that its consumption should also elevate brain tryptophan and serotonin.We now report that the elective consumption of protein-containing diets may or may not be followed by increases in brain tryptophan and 5-hydroxyindoles, and that this effect of food consumption on the brain is best corre- lated not with plasma tryptophan concentration, per se, but with the ratio of plasma tryptophan to five other neutral amino acids that presumably compete with it for uptake into the brain.Male Sprague-Dawley rats (Charles River Breeding Laboratories) were housed as described in (3). At 9 p.m. the evening before an experiment, the rats were placed in clean cages and deprived of food. Between noon and 3 p.m. the next day, groups of six to eight animals were given free access to one of the following diets: (i) diet 1, a carbohydrate diet (3); (ii) diet 2, diet 1 supplemented with 18 percent casein, dry weight; (iii) diet 3, diet 1 supplemented with an artificial amino acid mixture similar to casein in amino acid content (5), 18 percent dry weigh; (iv) diet 3, but lacking specific amino acids as described below. In all experiments, animals consumed approximately 5 to 7 g of food during the first hour and 3 to 5 g during the second hour. Control rats were fasted and were killed at the beginning of the first hour of the experiment (0-hour control), or 1 or 2 hours later (1-hour and 2-hour controls, respectively). Experimental rats were killed 1 or 2 hours after diet presentation. Blood and brains were collected and prepared as described (3...

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines

“…Springer does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Springer. 14 accurate index of the effect of treatments that modify plasma LNAA pattern on the competitive uptake of TRP and TYR into brain (Fernstrom and Wurtman 1972;Fernstrom and Faller 1978;Fernstrom 1983). 5HTP and DOPA were measured in hypothalamic samples by HPLC/electrochemical detection (using α-methyldopa as an internal standard), as previously described (Choi et al 2009).…”

“…And, the effects of the amino acid mixtures studied on the competitive BBB uptake of TRP and TYR into the brain were evaluated by measuring plasma levels of the BCAA and aromatic amino acids [TRP, TYR, and phenylalanine (PHE)], and expressing these values as ratios of TRP and TYR to the sum of the other, competing LNAA. Such TRP and TYR ratios are reliable predictors of the effects on brain TRP and TYR concentrations of ingested amino acids and dietary proteins (Fernstrom and Wurtman 1972;Fernstrom et al 1986;Fernstrom and Fernstrom 1995b). Finally, TRP and TYR concentrations were measured in cortex, as changes in this region are like those observed in other brain regions (including hypothalamus) under similar study conditions (e.g.…”

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

“…The role of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in learning and memory has been demonstrated in both humans and animals (Buhot 1997;Buhot et al 2000;Meneses 1999;Riedel et al 1999;Schmitt et al 2000). Studies using the method of acute tryptophan depletion (ATD), which results in lower peripheral and central levels of tryptophan and 5-HT Fernstrom and Wurtman 1997;Gessa et al 1974;Moja et al 1989;Stancampiano et al 1997), consistently report impaired memory in healthy volunteers (Park et al 1994;Riedel et al 1999;Sambeth et al 2007;Schmitt et al 2000) and rats (Jans et al 2007a;Lieben et al 2004b;Rutten et al 2007). More specifically, ATD studies have shown impairments of long-term memory performance (Riedel et al 2002) and reduced ability to actively recall, as well as recognize, words from a previously presented word list (Riedel et al 1999).…”

Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation

“…This uptake process depends on a competitive, saturable transport carrier shared by tryptophan and several other large neutral amino acids (LNAAs), and the branchedchain amino acids. 13,14 Because of competitive transport, brain tryptophan uptake and, ultimately, serotonin synthesis are influenced by plasma concentrations not only of tryptophan but also of the other LNAAs. The plasma ratio of the concentration of tryptophan to the sum of the concentrations of the other LNAAs (the plasma tryptophan ratio), which summarizes this competitive relation, has been proven to be a useful and reliable predictor of brain tryptophan uptake and central serotonin synthesis.…”