Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

ABSTRACT Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Is there a relationship between tryptophan dietary intake and plasma levels of indoxyl sulfate in chronic kidney disease patients on hemodialysis? / Há relação entre ingestão alimentar de triptofano e níveis plasmáticos de indoxil sulfato em pacientes renais crônicos em hemodiálise?

Abstract Introduction: Gut microbiota is involved in generation of uremic toxins in chronic kidney disease (CKD) patients on hemodialysis (HD), like indoxyl sulfate (IS) that is originated from tryptophan amino acid fermentation. Objective: To evaluate the tryptophan intake by chronic renal failure patients on HD and its possible relationship with IS plasma levels. Methods: Participated of the study 46 patients with CKD on HD regular program (56.5% men; 52.7 ± 10.3 years; 63 (32.2-118.2) months on HD; BMI 25.6 ± 4.9 kg/m2). The tryptophan intake was evaluated by a 24-hours dietary recall (R-24h) performed on 3 different days. Routine biochemical tests and anthropometric measurements were evaluated. IS plasma levels were determined by High Performance Liquid Chromatography (HPLC) with fluorescent detection and the interleukin-6 (IL-6) plasma levels by immunoenzymatic method (ELISA, Enzyme Linked Immunosorbent Assay). Results: The average of tryptophan intake was according to recommendation, but IS plasma levels (35.0 ± 11.9 mg/L) were elevated, however according to the EUTox values for uremic individuals. There was no correlation between the tryptophan intake and IS plasma levels. However, there was positive correlation between protein intake and tryptophan and variables used to evaluate lean body mass, and moreover, IS levels were positively associated with IL-6 (r = 0.6: p = 0.01). Conclusion: The present study suggests that tryptophan dietary intake may not be a determinant factor to IS levels. However, it suggests that gut microbiota may play an important role in systemic inflammation in patients with CKD.

Resumo Introdução: A microbiota intestinal está envolvida na geração de toxinas urêmicas presentes nos pacientes com doença renal crônica (DRC) em hemodiálise (HD) como indoxil sulfato (IS), formado a partir da fermentação do aminoácido triptofano. Objetivo: Avaliar a ingestão de triptofano alimentar pelos pacientes renais crônicos em HD e sua possível relação com os níveis plasmáticos de IS. Métodos: Participaram do estudo 46 pacientes com DRC em programa regular de HD (56,5% homens; 52,7 ± 10,3 anos; 63 (32,2-118,2) meses em HD; IMC 25,6 ± 4,9kg/m2. A ingestão de triptofano foi avaliada por meio do recordatório alimentar de 24 (R-24h) realizado em três diferentes dias. Exames bioquímicos de rotina, bem como a avaliação antropométrica foram avaliados. Os níveis plasmáticos de IS foram determinados por cromatografia líquida de alto desempenho (HPLC) com detecção fluorescente e as concentrações plasmáticas de interleucina-6 (IL-6) pelo método imunoenzimático (ELISA, Enzyme Linked Immunosorbent Assay). Resultados: A ingestão média de triptofano estava dentro do recomendado, já os níveis plasmáticos de IS (35,0 ± 11,9mg/L) estavam elevados, porém de acordo com os valores da EUTox para indivíduos urêmicos. Não houve correlação entre a ingestão de triptofano e os níveis plasmáticos de IS. Contudo, houve correlação positiva entre ingestão de proteína e triptofano e variáveis que avaliam massa magra e, além disso, os níveis IS foram positivamente associados com os de IL-6 (r = 0,6: p = 0,01). Conclusão: O presente estudo sugere que a ingestão alimentar de triptofano pode não ser um fator determinante dos níveis de IS. No entanto, sugere que o intestino pode ter importante papel na inflamação sistêmica presente nos pacientes com DRC.

Desempenho e rendimento de carcaça em frangos de corte de um a 46 dias alimentados com dietas contendo diferentes níveis de valina e reduzido teor proteico / Performance and carcass yield of broilers from 1 to 46 days fed diets containing different levels of valine and reduced protein content

Este estudo teve como objetivo avaliar as relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta (PB) e os efeitos dessa redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos seguindo modelo inteiramente ao acaso, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado conforme os níveis de proteína bruta e aminoácidos (AAs) recomendados por Rostagno et al . (2011), e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com cinco níveis equidistantes em intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 (dietas até 21 dias) e de 0,64:1 e 0,92:1 (dietas após 21 dias). As seguintes características de desempenho foram avaliadas: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade, seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05) para nenhuma característica avaliada. A redução proteica piorou a conversão alimentar dos animais (P≤0,05) até os 21 dias. Os resultados sugerem que os níveis de valina utilizados não afetam o desempenho dos animais, apenas o rendimento de peito e que, portanto, a redução proteica não é recomendada durante as três primeiras semanas de criação.

This study aimed to evaluate valine:lysine ratios in diets with reduced content of crude protein and the effects of this reduction on the performance of broiler chickens. 1200 male chicks were used following a complete randomized design with six replicates of six treatments (except control, with 10 replicates), each one with 30 chicks. The control treatment (T1) was formulated following levels of crude protein (CP) and the amino acids (AAs) recommended by Rostagno et al. (2011), and the other treatments (T2 to T6) had reduced levels of CP (4 % compared to control) and varied in proportion valine:lysine, with 5 levels at equidistant intervals 0.07:1 ranging from 0.63:1 to 0.91:1 (up to 21 days) and from 0.64:1 to 0.92:1 (after 21 days). The performance characteristics measured were: weight gain, feed intake, feed conversion, viability and productive efficiency index. At 46 days six animals per replicate were slaughtered for evaluation of carcass and commercial cuts. The different valine:lysine ratios did not affect animal performance (P>0.05). Reducing protein impaired feed conversion (P≤.05) up to 21 days. The results suggest that levels of valine used did not affect the broilers' performance, however, breast meat yield and reduced protein are not recommended during the first three weeks.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus. .

Dose-dependent response of central dopaminergic systems to buspirone in mice.

Buspirone, a partial agonist of 5-hydroxytryptaminelA autoreceptors, preferentially blocks the presynaptic rather than the postsynaptic D2 dopamine (DA) receptors. Behavioural effects of a wide dose range of buspirone were therefore studied in mice. Buspirone at 0.625 to 5 mg/kg ip induced stereotyped cage climbing behaviour which was antagonized by pretreatment with haloperidol, alpha-methyl-p-tyrosine and small doses of apomorphine. Buspirone at 10, 20 and 40 mg/kg ip induced catalepsy and antagonized oral stereotypies induced by high doses of apomorphine and methamphetamine and apomorphine-induced cage climbing behaviour. The findings indicate that buspirone at 0.625 to 5 mg/kg selectively blocks the presynaptic mesolimbic D2 DA autoreceptors and releases DA which stimulates the postsynaptic mesolimbic D2 and D1 DA receptors and induces cage climbing behaviour. Buspirone, at 10, 20 and 40 mg/kg blocks the postsynaptic striatal and mesolimbic D2 and D1 DA receptors. Pretreatment with 1-tryptophan, dexfenfluramine and fluoxetine antagonized buspirone induced cage climbing behaviour and potentiated buspirone induced catalepsy. Pretreatment with trazodone, mianserin and p-chlorophenylalanine potentiated buspirone induced cage climbing behaviour and antagonized buspirone induced catalepsy. The results indicate that drugs which influence the activity of central serotonergic systems modulate the intensity of buspirone induced cage climbing behaviour and catalepsy.

Dietary requirement of tryptophan for growth and survival of the Indian major carp, Cirrhinus mrigala (Hamilton-Buchanan) fry.

The experimental diets (40% protein) contained graded levels of tryptophan (0.60, 0.75, 1.00, 1.25, 1.50, 1.75%) of dietary protein. Each test diet was fed to triplicate groups of mrigal fry twice daily at 10% of the total biomass for 8 weeks. The dietary tryptophan requirement was estimated by plotting weight gain against dietary levels of tryptophan using two separate regression equations, the point of intersection of two equations was taken as optimum level, which occurred at 0.48% of the diet (1.20% of dietary protein).

Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

L-tryptophan [TRP] is widely used to enhance serotonin mediated brain functions. In the present study effects of oral administration of TRP [100mg/kg] daily for 5 weeks, were investigated on the food intake, growth rate and brain indoleamine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine [5-HT] were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid [5-HIAA] were not significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration though increases brain 5-HT metabolism and turnover but functional responses to 5-HT are not necessarily increased

Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan & in the serum of patients of neurodegenerative & psychiatric disorders.

Since binding sites for morphine, nicotine and strychnine exist in the brain, it is possible that they may have some role in neuronal function. The presence/variation in the levels of these alkaloids in the brain of rats fed tryptophan and tyrosine, and in the serum of patients with some neurodegenerative and psychiatric disorders were studied. Brain of rats loaded with tyrosine (500 mg/kg b wt X 14 days) showed increased amounts of morphine, while that from animals loaded with tryptophan (in the same dose) showed presence of strychnine and increased amounts of nicotine. Strychnine is being reported in mammalian brain for the first time. Serum of patients with epilepsy, Parkinson's disease (PD) and manic depressive psychosis (MDP) was also examined for the presence of these alkaloids. Serum of control subjects did not show the presence of any of these alkaloids, while that of all 3 patients groups contained strychnine. Morphine was present only in the serum of patients of MDP. Nicotine was present in trace amounts in the serum of all these patients. Presence of these alkaloids in the serum of patients of neurodegenerative and psychiatric disorders is being reported for the first time, to the best of our knowledge.

Effects of caffeine and tryptophan on rectal temperature, metabolism, total exercise time, rate of perceived exertion and heart rate

Stimulant properties during exercise have been attributed to cafeine (CAF) and tryptophan (Trp). The purpose of the present study was to investigate the effects of CAF and Trp ingestion on rectal temperature (Tre), total exercise time (TET), oxygen consumption (VO2), carbon dioxide production (VCO2) pulmunary ventilation (VE), heart rate (HR) and rate of perceived exertion (RPE) during exercise on a cycle ergometer at 80 percent of maximal work load, in eight halthy male volunteers. Each subject abstained from caffeine for 48 h and from animal-derived foods for 36 h before each experiment. Aerobic capacity was determined on the first day. In consecutive trials, conducted in a double-blind, randomized, crossed-over manner, each subject recived capsules containing CAF (10mg/Kg), Trp (1.2g), a combination of the two (CAF + TRP), and lactose (PLA), 1 h before exercise. Plasma CAF concentration (PC) was measured by high performance liquid chromatography (HPLC), before (basal concentration) and 1 and 2 h after ingestion of the capsules. At both times after CAF or CAF + Trp ingestion, the PC was elevated compared with the basal concentration (P < 0.05). During exercise, significant increases occured with time in Tre, TET, VO2, VCO2, VE, HR and RPE (P < 0.01) while no significant difference was observed when CAF or CAF+ Trp were compared with control values. Under the conditions of this study, CAF and/or Trp did not affect the physiological parameters measured before, during or after exercise at 80 percent of maximal work load