The aim of this study was to determine the differences between two groups of adolescents with metabolic syndrome (MetS) and normal controls in relation to brain serotonergic activity through intensity-dependent auditory-evoked potentials (IDAEPs) and plasma free fraction of L-tryptophan. Eighteen adolescents with MetS and thirteen controls were studied. Free fraction, bound and total plasma L-tryptophan, glucose, cholesterol, triglycerides, HDL-cholesterol, albumin and IDAEPs were determined. Glycemia, triglycerides were significantly elevated, and HDL-cholesterol in plasma was significantly reduced. Free fraction and free fraction/total L-tryptophan ratio were decreased. The slope of the amplitude/stimulus intensity function of the N1/P2 component significantly increased in adolescents with MetS. Decrease of free fraction of L-tryptophan in plasma and increase of the slope of the N1/P2 component suggest a low brain serotonin tone. Cortex responses are regulated by serotonergic innervations and may show a different behavior in young patients with MetS. Therefore, the slope of the N1/P2 component along with the free fraction of L-tryptophan in plasma, indicate that in adolescents with MetS the state of serotonergic brain activity is depressed and possibly related to psychiatric disorders.

The aim of this study was to determine whether intrauterine malnutrition (IUM) produces a change in the expression of tryptophan-5-hydroxylase (TPH) 1 and/or 2 as the primary mechanism to explain the observed chronic cerebral acceleration of the synthesis of 5-hydroxytryptamine (5-HT). We used an IUM model and controls with ages of 1, 15 and 21 days. The brainstem was obtained to determine L-tryptophan, 5-HT and TPH activity. Expression of TPH1 and TPH2 via specific antibodies for each was also evaluated by immunocytochemistry and Western blot. Malnourished offspring had a significant elevation of L-Trp, TPH activity and 5-HT in the brainstem. Both isoforms (1 and 2) of TPH were expressed from birth in both groups; however, TPH1 expression was significantly higher in offspring with IUM in relation to the controls. Importantly, these malnourished offspring showed reduced expression of TPH2 compared to controls. It was confirmed that IUM produces an increase in 5-HT in the brainstem and also showed increased expression of TPH1 at birth, with decreased expression of TPH2. These findings together allow us to propose that chronic elevation of synthesis of 5-HT observed in the brain of the offspring with IUM is probably due to a change in the expression and activity of TPH1 induced from fetal life.

The aim of this study was to determine whether intrauterine growth restriction produces an increase of dihydropteridine reductase activity as a compensatory mechanism that maintains the necessary concentration of cofactor, tetrahydrobiopterin, during accelerated brain serotonin biosynthesis. Intrauterine growth-restricted offspring and controls were used. On days 1, 10, 15 and 21 of life, the brainstem was dissected and l-tryptophan, serotonin, tryptophan-5-hydroxylase and dihydropteridine reductase activities were determined. Intrauterine growth-restricted pups showed a significant increase of l-tryptophan, 5-hydroxytryptamine, tryptophan-5-hydroxylase and also dihydropteridine activity in the brainstem in comparison to normal pups. These results confirm that intrauterine growth restriction produces an increase of serotonin biosynthesis in the brainstem. This is accompanied by an increase in dihydropteridine activity that appears to be a compensatory mechanism to maintain sufficient tetrahydrobiopterin for the donation of electrons during the accelerated synthesis of brain serotonin in intrauterine growth-restricted rats.

This review aimed to describe and comment on how experimental intrauterine nutritional stress in animals produced some changes in tryptophan-5-hydroxylases (TPH) 1 and 2 in the brain and other key proteins such as plasma albumin, and how the intrauterine nutritional stress could produce long-lasting alterations in serotonin function in the brain of human infants.