Free tryptophan as an indicator of brain serotonin synthesis in infants

Manjarrez-Gutiérrez, Gabriel; Contreras, Juan S.; Chagoya, G.; Hernández-R, Jorge

doi:10.1016/s0887-8994(97)00163-x

Cited by 25 publications

(31 citation statements)

References 47 publications

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“…Other studies described an elevation of FFT and its ratio to total tryptophan (FFT/total tryptophan) in IUGR children (Manjarrez et al, 1998;Hernandez-Rodriguez et al, 2009). Interestingly, our results also described a higher FFT/total tryptophan ratio in SGA piglets.…”

Section: Discussionsupporting

confidence: 79%

“…As serotonin enhances growth hormone secretion, which in turn stimulates IGF production (Musumeci et al, 2013), we hypothesise that this altered endocrine balance is reflected in an altered intestinal distribution of enterochromaffin cells. In the blood circulation, the free fraction of tryptophan (FFT) is an important marker for encephalic 5-HT synthesis, whereas most of 5-HT in blood is derived from the gastrointestinal tract (Erspamer and Testini, 1959;Tagliamonte et al, 1973;Manjarrez et al, 1998). Intriguingly, infants and rats suffering from IUGR show elevated plasma FFT levels compared with normal weight (NW) infants and littermates (Hernandez et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets

Willemen

Che

Dewilde

et al. 2014

Animal

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Perinatal mortality is high among small-for-gestational age (SGA) piglets and continues to be an economic burden and threat to animal welfare. As the physiological role of serotonin (5-hydroxytryptamine, 5-HT) in perinatal development and gastrointestinal function in the pig remains unknown, the aim of this study was to assess the enteric distribution of 5-HT cells and to determine 5-HT together with its precursor tryptophan in the serum of perinatal normal and SGA piglets. For this purpose, proximal and distal parts of the small intestine (SI) were processed for immunohistochemical analysis to assess the presence of 5-HT endocrine cells. Serum 5-HT was measured with ELISA, whereas its precursor, that is, the free fraction of tryptophan (FFT) together with albumin-bound tryptophan and total tryptophan, were analysed with HPLC in postnatal piglets. In addition, the morphological growth patterns of the different intestinal tissue layers of both normal and SGA piglets were stereologically analysed. The stereological volume density of 5-HT enteroendocrine cells showed a significant interaction effect between age and region. Indeed, the amount of 5-HT cells in both the proximal and distal part of the SI tended to decrease according to age, with the lowest values detected at day 3 postpartum. No differences could be observed related to BW. Interestingly, the serum concentration of 5-HT was higher in normal piglets compared with SGA piglets. Moreover, the ratio of FFT to total tryptophan was significantly affected by age and BW. Normal piglets had, on average, a lower FFT/total tryptophan ratio compared with SGA piglets. An approximate linear decrease was observed with increasing age. Finally, the immaturity of the intestinal system of the SGA piglets was not reflected in altered volume densities of the different intestinal layers. To conclude, although no BW effect could be detected in the distribution of enteric 5-HT cells, serum 5-HT and the ratio of FFT to total tryptophan ratio showed significant differences between normal piglets and their SGA littermates.Keywords: low birth weight, pig, serotonin, serum, small intestine ImplicationsThe use of hyperprolific sows in the pork industry increases the prevalence of prenatal growth-restricted piglets, characterised by reduced survival rates. Serotonin is prominently present in the gastrointestinal system and regulates feeding behaviour and BW. This study investigated the enteric distribution of serotonin cells and the concentration of this hormone along with its precursor tryptophan in the serum of perinatal SGA and normal littermates. These results -combined with the morphological analysis of the small intestine -will give insight into the endocrine programming and morphological adaptations of the small intestine of SGA piglets.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets

Willemen

Che

Dewilde

et al. 2014

Animal

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“…This might increase the vulnerability of small-for-age neonates, which exhibit an inappropriate acceleration of serotonin synthesis during hypoxia (9). Furthermore, independent of the occurrence of hypoxic episodes, 5-HT 2 receptor activation might work together with altered respiratory muscle function (20) to impair ventilation in growth-retarded neonates with increased serotonin synthesis (8).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the likelihood of 5-HT 2 receptors being activated increases with the concentration of serotonin synthesized or released centrally. This concentration has been reported to be abnormally elevated in neonates with intrauterine growth retardation (8) and notably during hypoxia (9). Furthermore, although serotonin acting at 5-HT 2 receptors might be benefi-cial to adults suffering from pathologic apneas in that it decreases the duration of deep slow-wave sleep (10), this mechanism might be inefficient in the neonate (11).…”

mentioning

confidence: 99%

5-HT2A/2C Receptor–Mediated Hypopnea in the Newborn Rat: Relationship to Fos Immunoreactivity

Cayetanot¹,

Gros²,

Larnicol³

2001

Pediatr Res

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Previous data derived from anesthetized, decerebrate, or in vitro preparations suggested that 5-HT 2 receptor activation might be responsible for respiratory dysfunction. Such a mechanism has not yet been documented in the intact animal, but might be of clinical relevance to the apneic spells of the premature infant. In the present investigation on conscious newborn rats we analyzed the respiratory response to the activation of 5-HT 2A/2C receptors by the agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and we delineated central structures possibly involved in this response, using Fos expression as a marker of neuronal activation. We demonstrated that intraperitoneal injection of 5 mg/kg DOI produced a long-lasting decrease in respiratory frequency and tidal volume, which could be blocked by the antagonist ritanserin. Fos immunohistochemistry suggested that the rostral ventrolateral medulla and the lateral paragigantocellular nucleus might have a key role in the respiratory response to 5-HT 2 receptor activation. In addition, double immunostaining for Fos and tyrosine hydroxylase suggested that the contribution of catecholaminergic neurons to this response might be modest and indirect. Serotonin (5-hydroxytryptamine; 5-HT) acting at 5-HT 2 receptors has been involved in the neuromodulation of a broad spectrum of functions ranging from mental processing to autonomic regulation (1). 5-HT also interferes with breathing control, via central and peripheral 5-HT 2 receptors, and variable responses have been reported. In vitro studies on brain stem-spinal cord preparations isolated from the newborn rat indicated that central 5-HT 2A receptor mechanisms may exert facilitating influences on respiration, by activating spinal respiratory motoneurons (2) and increasing the frequency of rhythmic respiratory discharge (3). In contrast, in adult anesthetized rats, the activation of 5-HT 2 receptors located at the periphery has been involved in decreases in phrenic nerve activity and lung compliance observed during apnea induced by 5-HT (4). In decerebrate newborn rats, the application of 5-HT 2A/2C receptor agonists to the floor of the fourth ventricle elicited a bradypnea (5), reminiscent of the decrease in frequency of respiratory-like activity that followed bath application of 5-HT 2C receptor agonists to in vitro preparations (3). Furthermore, the finding that 5-HT 2A/2C receptor agonists inhibit hypoglossal inspiratory activity in isolated brain stemspinal cord preparations led to the hypothesis that 5-HT 2 receptors may be involved in the genesis of obstructive apneas in newborns with increased 5-HT biosynthesis (2, 6). Nevertheless, the depressant influence of 5-HT 2 receptor activation on hypoglossal activity has not been confirmed on medullary rhythmic slice (7). Altogether, those findings suggest that 5-HT 2 receptor mechanisms might influence the network devoted to respiratory control at multiple levels and that the response to 5-HT 2 receptor activation in the intact animal may not be definitely deduced...

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“…Infants with IUGR, also show an elevation of FFT in their plasma [7,19] , which suggests an increased transport of this precursor amino acid with enhancement of serotonin synthesis and activity in their brains [7,19,20] . In preliminary studies in rats with IUGR, a minor capacity of plasma albumin to bind 3H L-Trp was observed, as compared mole to mole to albumin from normal controls, suggesting that binding kinetics of L-Trp to albumin could be significantly modified.…”

Section: Introductionmentioning

confidence: 99%

Another Abnormal Trait in the Serotonin Metabolism Path in Intrauterine Growth-Restricted Infants

et al. 2008

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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.

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Free tryptophan as an indicator of brain serotonin synthesis in infants

Cited by 25 publications

References 47 publications

Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets

Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets

5-HT2A/2C Receptor–Mediated Hypopnea in the Newborn Rat: Relationship to Fos Immunoreactivity

Another Abnormal Trait in the Serotonin Metabolism Path in Intrauterine Growth-Restricted Infants

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