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.

Barrel formation is delayed in nutritionally restricted rats. The underlying cause of such delay is yet unclear. Because barrels appear upon the arrival of somatosensory thalamo-cortical afferents and the reorientation of the dendritic arborizations of cortical spiny stellate neurons, it is likely that at least one of these processes is altered by nutritional restriction. Also, the serotoninergic afferent system has been implicated in regulating barrel segregation and growth during early postnatal life. We then evaluated the pattern of immunostaining of the serotonin transporter (SERT) and of the serotonin receptor 1B (5-HT(1B)), as well as the growth and arrival time of somatosensory thalamo-cortical afferents, to infer the contribution of these elements in the delayed formation of barrels observed in nutritionally restricted rats. It was found that the rates of development and the segregation of thalamo-cortical fibers were normal in nutritionally restricted rats. SERT, but not 5-HT(1B) immunoreactivity, was decreased in the primary somatosensory cortex during barrel specification. The availability of both proteins in nutritionally restricted rats was lower than that observed in their well fed counterparts at later developmental times. It is concluded that the delayed formation of barrels observed in nutritionally restricted rats is due to a retarded reorientation of dendritic arbors of cortical neurons. This might happen as a secondary effect of decreasing the availability of SERT and/or increasing the availability of 5-HT(1B) receptor early in postnatal life.

Background: The present study was aimed to obtain information on the interaction kinetics of L-tryptophan (L-Trp) with plasma albumin from normal, intrauterine growth-restricted (IUGR) and nutritionally recovered (NR) newborn infants. Methods: A case study cohort was planned in 37 newborns during the first 3 months of life. At birth two groups were formed. The first group included 20 newborns with IUGR. The control group (C) included 17 appropriate for gestational age newborns. At 30 days of age, 9 infants of the IUGR group showed a return to normal of the anthropometric parameters, these infants formed the NR group. Free, bound and total L-Trp were measured. To assess binding kinetics albumin was freed of fatty acids and tested in mole to mole samples from IUGR, NR and control babies. Results: Plasma free L-Trp was increased, K_d (dissociation constant) elevated and B_max (maximal binding)decreased in IUGR patients up to postnatal day 90. These changes remained even after nutritional recovery. Conclusions: Abnormal kinetics of L-Trp binding to albumin explains the increased availability of this precursor amino acid in the plasma of IUGR infants. This finding corroborates previous results in IUGR rats and newborn babies, indicating enhanced potential for brain serotonergic synthesis.

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.