International Journal of Tryptophan Research最新文献

{"title":"Tryptophan Supplementation Reduces Schizophrenia-Like Symptoms in Apomorphine Treated Rats: Role of D2, GABA, and Glutamate Receptor Expression.","authors":"Shazia Nawaz, Sadia Basharat Ali, Rushda Afroz, Huma Ikram, Faisal Khan, Darakhshan Jabeen Haleem","doi":"10.1177/11786469261478896","DOIUrl":"10.1177/11786469261478896","url":null,"abstract":"<p><p>Schizophrenia is a multifaceted neuropsychiatric disorder characterized by disruptions in dopaminergic, GABAergic, and glutamatergic signaling pathways. While conventional antipsychotics primarily target dopamine D2 receptors, exhibit limited efficacy to alleviate cognitive deficits and negative symptoms and are associated with extrapyramidal side effects. Tryptophan (Trp), the essential amino acid precursor to serotonin, is critical modulator of these circuits. Serotonin acts as a brake on dopamine release and receptor activity. This study investigates the therapeutic potential of Trp supplementation in reducing schizophrenia-like symptoms in apomorphine-treated rats, focusing on the mRNA expression of D2, GABA, and glutamate receptors in nucleus accumbens and caudate. Apomorphine, a dopamine agonist, induces hyperdopaminergic activity, mimicking schizophrenia-like behaviors. In the present study, rats were divided into control, apomorphine-treated, Trp-supplemented and apomorphine plus Trp treated groups. Trp was administered at two different doses (25 and 50 mg/kg). Behavioral assessments were conducted in novel and familiar environments, Morris water maze and elevated plus maze to evaluate motor activity, learning and memory, and anxiety respectively. Results demonstrated that Trp supplementation significantly ameliorated the schizophrenia-like symptoms induced by apomorphine, exhibiting a distinct biphasic pattern: the 25 mg/kg dose was consistently more effective than the 50 mg/kg dose. Specifically, the low dose Trp reduced hyperactivity, improved cognitive performance and anxiolytic effects. In contrast, the 50 mg/kg dose showed a diminished therapeutic effect, likely due to competitive kynurenine pathway activation. Molecular analysis showed that optimal tryptophan treatment decreased the mRNA expression of D2 receptors, enhanced GABA receptor mRNA expression, and stabilized glutamate receptor mRNA levels in key brain regions. These findings suggest that low dose tryptophan supplementation may offer a promising adjunctive treatment for schizophrenia by restoring transcriptional balance of critical neurotransmitter systems.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261478896"},"PeriodicalIF":4.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Kynurenine Metabolite 3-Hydroxykynurenine is Associated With Risk of Heart Failure in Patients With Predominantly Stable Coronary Artery Disease.","authors":"Anders Lund, Jan Erik Nordrehaug, Kjell-Christian Flo, Kyrre Hasås Toresen, Christian Alsing, Adrian McCann, Per Magne Ueland, Ottar Nygård, Lasse M Giil","doi":"10.1177/11786469261479281","DOIUrl":"https://doi.org/10.1177/11786469261479281","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and immune activation contribute to the development and progression of heart failure (HF). The kynurenine pathway, linking tryptophan metabolism to inflammation, oxidative stress, and cell death by way of its metabolites (kynurenines), has not been studied as a pathway associated with risk for incident HF.</p><p><strong>Aims: </strong>To investigate whether kynurenine metabolites are associated with incident HF in patients with predominantly stable coronary artery disease.</p><p><strong>Methods: </strong>Serum kynurenine metabolites were quantified in 3841 patients who underwent elective coronary angiography for evaluation of chest pain. Fasting was not routine. Patients with established HF at baseline were excluded. The hazard for incident HF was estimated using Cox regression, adjusted for age, gender, current smoking, diabetes, hypertension, previous myocardial infarction, body mass index, glomerular filtration rate, troponin T, left ventricular ejection fraction, and resting heart rate.</p><p><strong>Results: </strong>During follow-up, 221 participants developed HF. Higher serum concentrations of 3-hydroxykynurenine (HK) were associated with increased HF risk (adjusted HR 1.31, 95% CI 1.07-1.46, <i>P</i> < .001).</p><p><strong>Conclusion: </strong>Higher plasma HK was independently associated with incident HF in patients with predominantly stable coronary artery disease. These findings support a possible link between kynurenine pathway activity and future HF risk, but the underlying mechanisms and clinical implications remain to be established.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261479281"},"PeriodicalIF":4.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Screening of Tryptophan Metabolism Identifies Site- and Microbiota-Dependent Signatures of Tryptophan Utilization in Experimental Colitis.","authors":"Lina Wehkamp, Abrar I Alsaadi, Danielle M M Harris, Meiping Yu, Taous Mekdoud, Johanna Bornhäuser, Eva Springer, Clara Gilloteau, Anant A Pothakamury, Jaclyn D Smith, Brenita C Jenkins, Martina Guggeis, Felix Sommer, Silvio Waschina, Philip Rosenstiel, Stefan Schreiber, Melanie R McReynolds, Konrad Aden","doi":"10.1177/11786469261472316","DOIUrl":"10.1177/11786469261472316","url":null,"abstract":"<p><strong>Background: </strong>Altered tryptophan (Trp) metabolism and disrupted nicotinamide adenine dinucleotide (NAD⁺) synthesis are hallmarks of IBD, yet how intestinal microbiota contribute to these metabolic shifts during intestinal inflammation remains poorly understood.</p><p><strong>Methods: </strong>We used targeted metabolomics to systematically profile Trp- and NAD⁺-related metabolites across multiple biological compartments - including tissues, luminal contents, stool and serum - in mice treated with dextran sulfate sodium (DSS) alone or in combination with a broad-spectrum antibiotic (ABX) cocktail.</p><p><strong>Results: </strong>Microbial depletion significantly attenuated colitis and increased host Trp bioavailability, implicating the gut microbiota as a competitive Trp consumer. In DSS colitis, Trp degradation along the kynurenine pathway (KP) was exaggerated but blocked at the key KP enzyme quinolinate phosphoribosyltransferase (QPRT), resulting in mucosal NAD(H) depletion. ABX co-treatment normalized metabolite conversion along the KP and restored mucosal NAD(H) levels, revealing a dual role of the gut microbiota during colitis: while they compete with the host for Trp utilization, they simultaneously shape host KP regulation and NAD⁺ de novo synthesis, supporting host energy homeostasis.</p><p><strong>Conclusion: </strong>Our findings demonstrate that mucosal NAD⁺ de novo synthesis is a microbially regulated metabolic process that alleviates intestinal inflammation and may represent a novel therapeutic target in IBD through modulation of the gut microbiota or their metabolites.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261472316"},"PeriodicalIF":4.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-Regulation of Anthranilic Acid Formation and Pro-Cognitive Effect of Indoleamine 2,3-Dioxygenase Inhibition.","authors":"Gregory Oxenkrug, Stefano Comai","doi":"10.1177/11786469261472317","DOIUrl":"10.1177/11786469261472317","url":null,"abstract":"<p><p>Inhibition of indoleamine 2,3-dioxygenase (IDO) is a promising therapeutic strategy for cognitive impairment in Alzheimer's disease (AD). The pro-cognitive effect is often attributed to restoring glycolysis by preventing tryptophan (Trp) conversion to kynurenine (Kyn). However, this overlooks the metabolic fate of Trp when IDO is blocked. Since IDO and tryptophan 2,3-dioxygenase (TDO) compete for the same substrate, inhibiting IDO may shunt Trp toward TDO, potentially increasing Kyn and its downstream catabolites. This commentary explores the hypothesis that the upregulation of anthranilic acid (AA), a Kyn catabolite, contributes to the cognitive benefits of IDO inhibition. Recent evidence shows elevated AA in animal models of AD and individuals with mild cognitive impairment and preclinical AD, where it may serve as an early biomarker. Notably, these elevations and the pro-cognitive effects of AA-modulating compounds like sodium benzoate exhibit sex-specificity, being more prominent in females. The mechanism may involve AA's dual action on G-protein coupled receptors: antagonism of GPR17 promotes myelination, while agonism of GPR109A may protect myelin from degradation. Preserving myelin integrity is critical, as demyelination is an early event in AD pathogenesis. We propose that AA upregulation is not merely a biomarker but part of a compensatory defense mechanism. Therefore, the pro-cognitive effect of IDO inhibition may be partly mediated by the subsequent shunting of Trp toward TDO and production of the myelin-preserving metabolite, AA. This reframes the therapeutic goal from reducing neurotoxic kynurenines to leveraging the protective potential of the entire pathway.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261472317"},"PeriodicalIF":4.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary Tryptophan Metabolites, Trace Element Status, and Autism Spectrum Disorder: An Integrated Metabolomics-Elementomics Study in Children.","authors":"Joško Osredkar, Kristina Kumer, Maja Jekovec Vrhovšek, Damjan Osredkar, Alenka France Štiglic, Gorazd Avguštin, Teja Fabjan","doi":"10.1177/11786469261467154","DOIUrl":"10.1177/11786469261467154","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with metabolic and environmental factors. We investigated associations between urinary tryptophan-pathway metabolites and essential/toxic trace elements in children with ASD and healthy controls. In a cross-sectional cohort of 216 children (149 ASD, 67 controls), urinary tryptophan metabolites were quantified by LC-MS/MS and normalized to creatinine. Trace elements were assessed by ICP-MS. Matching yielded 1:1 (n = 57/57) and 1:2 (n = 30/60) age- and sex-matched subsets. Correlations (Pearson or Spearman, FDR-adjusted) and group comparisons were performed; autism severity (CARS) was analyzed within ASD. Creatinine-normalized tryptamine, 5-hydroxyindoleacetic acid, and N-acetyltryptophan showed moderate, positive correlations with essential elements (Mg, Zn, Se; r ≈ 0.5-0.7; N-acetyltryptophan and IAA correlated modestly with toxic elements (Tl, Cs; r ≈ 0.3-0.4). Group differences in individual metabolites and elements were modest; however, the composite toxic element index was significantly lower in ASD (<i>P</i> = .002). CARS scores did not show robust, FDR-corrected associations. Essential trace elements are closely linked to tryptophan metabolism, suggesting cofactor-dependent modulation in ASD. N-acetyltryptophan may serve as a sensor for specific toxic elements. Intervention studies are warranted to clarify causality.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261467154"},"PeriodicalIF":4.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Downstream Kynurenine Pathway Metabolites in the Modulation of Cardiovascular Disease Development in Chronic Kidney Disease.","authors":"Magdalena Zabłudowska, Magdalena Kopańko, Beata Sieklucka, Krystyna Pawlak","doi":"10.1177/11786469261467158","DOIUrl":"10.1177/11786469261467158","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) represent a significant and escalating health challenge in patients with chronic kidney disease (CKD). In this population, the cardiovascular incidents are markedly elevated, and CVD represents the leading cause of mortality. The pathogenesis of CVD in the course of CKD is multifactorial, and some evidence indicates that disturbances in the kynurenine pathway (KP), the major route of tryptophan metabolism, can also play a significant role in this process. The enhanced activation of the KP and reduced clearance of its metabolites contribute to their accumulation during CKD progression, potentially exacerbating cardiovascular risk. Few data suggest that certain downstream KP metabolites, including 3-hydroxykynurenine (3-HKYN), quinolinic acid (QUIN), and anthranilic acid (AA), are associated with established CVD risk factors, while others, such as 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid (KYNA), exhibit more complex and ambiguous effects, with potential protective actions on the cardiovascular system. The aim of this review is to summarize current knowledge of the roles of individual downstream kynurenine (KYN) metabolites in the development of CVD in the CKD population. Since for some kynurenines there are only isolated or ambiguous reports in this field, the review has been completed with data on the contribution of downstream KYN metabolites in the development of CVD in the general population and in experimental models.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261467158"},"PeriodicalIF":4.9,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latent Cerebral Toxoplasma Gondii Infection Induces the Kynurenine Pathway and Production of Neurotoxic Metabolites.","authors":"Amir Mohamed Kezai, Mahmoudou Ba, Benjamin Hennart, Anais Jacquemart, Emilie Faivre, David Blum, Delphine Allorge, Sabrina Marion","doi":"10.1177/11786469261461119","DOIUrl":"10.1177/11786469261461119","url":null,"abstract":"<p><p>The kynurenine pathway (KP) has been implicated in a broad range of neurological disorders. KP activation in brain resident immune cells, including astrocytes and microglia, contributes to the release of neuroactive metabolites with strong impact on neuronal functions. KP activation is triggered by inflammatory cues, however the contribution of chronic brain infections on KP activation remains poorly explored. Toxoplasmosis is 1 of the most common infections caused by protozoan parasites. Infection of immuno-competent individuals is characterized by bradyzoite-containing cyst development in neurons, leading to life-long chronic infections. Control of latent toxoplasmosis relies on an IL-12-induced T-cell derived IFNγ response, and results in a sustained inflammation of the brain characterized by activation of recruited and resident immune cells. Here, we investigated a possible link between induction of a persistent neuroinflammation induced by <i>Toxoplasma gondii</i> long-term infection, modulation of the KP and production of key neuroactive metabolites. Our findings demonstrate that chronic infection with either of 2 <i>Toxoplasma gondii</i> strains- causing encephalitis and the other inducing latency-leads to sustained activation of the KP, resulting in increased production of quinolinic acid, an excitotoxic metabolite known to have detrimental effects on neurons.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261461119"},"PeriodicalIF":4.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of Hypoxia and Kynurenine Pathway in Periodontal Inflammation.","authors":"Ardita Koci, Sivge Kurgan, Nur Balci, Zeliha Guney, Emrah Turkmen, Ceyhan C Serdar, Muhittin A Serdar, Elif Unsal","doi":"10.1177/11786469261457028","DOIUrl":"10.1177/11786469261457028","url":null,"abstract":"<p><p>The kynurenine pathway (KP), the primary route of tryptophan (TRP) metabolism, is influenced by inflammation and hypoxia and has been linked to immune dysregulation and oxidative stress. This study investigated the relationship between KP activity and hypoxia in periodontal inflammation, as well as their association with clinical periodontal parameters. A total of 23 systemically healthy patients with stage III, grade B periodontitis and 22 periodontally healthy individuals were included. Salivary and serum levels of tumor necrosis factor-alpha (TNF-α), hypoxia-inducible factor-1 alpha (HIF-1α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using ELISA. KP metabolites were analyzed via liquid chromatography-mass spectrometry. Results showed that salivary TNF-α, HIF-1α, and 8-OHdG levels were significantly higher in the periodontitis group (<i>P</i> < .05). Both salivary and serum kynurenine/tryptophan (KYN/TRP) ratios and picolinic acid (PA), along with salivary 3-hydroxykynurenine (3OHKYN) and serum kynurenine (KYN), were elevated in periodontitis (<i>P</i> < .05). In contrast, TRP levels in both saliva and serum were significantly reduced (<i>P</i> < .001). Correlation analyses revealed that TRP levels were negatively associated with periodontal disease severity, whereas the salivary KYN/TRP ratio, 3OHKYN, HIF-1α, 8-OHdG, and TNF-α were positively associated (<i>P</i> < .05). Strong correlations were observed between the saliva and serum compartments, with a strong positive relationship between salivary and serum TRP and a moderate correlation for the KYN/TRP ratios. Multivariate logistic regression identified salivary KYN/TRP ratio and HIF-1α as independent predictors of periodontitis after adjusting for age and gender, with male gender also emerging as a significant factor (<i>P</i> < .05). Overall, the findings suggest that KP alterations, hypoxia, and oxidative stress are closely interconnected in periodontal inflammation. However, due to the cross-sectional design, these associations should not be interpreted as causal. The KP and hypoxia pathways may serve as potential non-invasive biomarkers for periodontitis.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261457028"},"PeriodicalIF":4.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Treatment for ADHD Based on Recovery from Tryptophan-Induced Central Fatigue by Powerful Competitive Inhibition of L-System Amino Acid Transporter.","authors":"Takanobu Yamamoto, Bianca Koleda-Yamamoto","doi":"10.1177/11786469261453179","DOIUrl":"10.1177/11786469261453179","url":null,"abstract":"<p><p>Fatigability in attention deficit hyperactivity disorder (ADHD) is associated with the characteristic inattention behavior. Evidence has indicated that the administration of branched-chain amino acids (BCAAs) to Nagase analbuminemic rats (NARs), a fatigue-prone animal model of ADHD, diminishes central fatigue. This effect is accompanied by competitive inhibition at the L-system amino acid transporter (LAT), which takes tryptophan into the brain. We investigated whether dietary supplementation with BCAAs plus phenylalanine and methionine (BPM) or BCAAs plus 2-amino-2-norbornanecarboxylic acid (BCAAs + BCH) has the effect of synergistically improving central fatigue in rats and humans compared with BCAAs alone. NAR performed exercise duration for 420 minutes (5 out of 5 rats; n = 5/5) using BPM and 542 minutes (n = 5/5) using BCAA + BCH. These were significantly longer than when saline or BCAA alone were administered to rats. When administering BPM supplements to human subjects, they found an efficacy rate of 50% in reducing fatigue compared to a placebo, compared to 38% for BCAA alone. Central fatigue in rats and humans was caused by a common mechanism involving tryptophan as an inducing trigger, and BPM supplementation contributed to the strong amplification effect of competitive inhibition at the LAT, the addition of phenylalanine and methionine. These powerful nutritional strategies improved exercise performance and mood beyond the physiological limits of fatigue. BPM, the natural nutrients, can promote the improvement of ADHD symptoms in humans. Prior to treatment with conventional monoamine reuptake inhibitors, it is necessary to eliminate fatigue by BPM treatment, which is the causative basis of ADHD.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261453179"},"PeriodicalIF":4.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan's Journey Through Pregnancy: The Role of Serotonin.","authors":"Benoît Gendrot, Cathy Vaillancourt, Guillemette Fouquet","doi":"10.1177/11786469261449491","DOIUrl":"10.1177/11786469261449491","url":null,"abstract":"<p><p>Tryptophan is an essential amino acid required for protein synthesis and a precursor of key bioactive metabolites produced through the kynurenine, indole and serotonin pathways. Beyond its nutritional role, tryptophan metabolism critically regulates the nervous, immune and endocrine systems, coordinates circadian rhythms via melatonin, and exerts antioxidant effects. These processes are profoundly remodeled during pregnancy. Pregnancy represents a unique physiological state characterized by systemic adaptations, including changes in immunity and erythropoiesis, while the placenta emerges as a central organ coordinating fetal development, maternal-fetal exchanges, immune tolerance, and protection against external infections. Increasing evidence indicates that tryptophan availability and its downstream metabolites play key roles in maintaining maternal-fetal and placental homeostasis. In particular, serotonin, traditionally viewed as a neurotransmitter, has emerged as a locally produced signaling molecule in the placenta, impacting trophoblast development, placental vascularization, and immune modulation. Dysregulation of tryptophan metabolic pathways has been associated with pregnancy complications and adverse developmental outcomes. This review aims to provide an overview of tryptophan metabolism during gestation, with a specific focus on serotonin as a key factor in placental homeostasis. Targeting tryptophan-derived pathways may offer novel opportunities to improve maternal and neonatal health.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"19 ","pages":"11786469261449491"},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}