International Journal of Tryptophan Research最新文献

{"title":"Neuroactive Kynurenine Metabolite Alterations Unveil Novel Association to Locomotor Deterioration in Diabetic Neuropathy.","authors":"Alejandra Perez-Alvarez, Victor Salazar, Gustavo Bruges, Eva Vonasek, Antonio Eblen-Zajjur","doi":"10.1177/11786469251372797","DOIUrl":"10.1177/11786469251372797","url":null,"abstract":"<p><strong>Background: </strong>The effect of prolonged hyperglycemia on the sensory pathway of the nervous system has been the focus of numerous diabetes studies that aim at understanding the pathophysiology of the underlying inflammatory condition and neuropathy. In this study, we investigate the effects of prolonged hyperglycemia on the motoneurons of the ventral horn of the spinal cord, a lesser-studied area of the nervous system, with a focus on alterations in the Kynurenine Pathway (KP) as potential factors contributing to the induction, progression, and/or chronicity of diabetic neuropathy.</p><p><strong>Methods: </strong>KP metabolites were identified and assessed by immunohistochemistry in cross-sections of the lumbar spinal cord of type 2 diabetes (T2D) streptozotocin-induced (STZ) adult Sprague-Dawley rats.</p><p><strong>Results: </strong>Neuropathy, hyperglycemia, and gait alterations were associated to myelin loss in the spinal cord. KP metabolites were identified in glia, motoneuron, and non-motoneuron. The KP induction, as evidenced by enhanced L-kynurenine (L-KYN) fluorescence, appears to be associated with increased levels of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Notable differences in fluorescence merging of L-KYN with IFN-γ and TNF-α, of Quinolinic acid (QUIN) with 3-Hydroxykynurenine (3-HK), and of QUIN with advanced glycation end products (AGEs) were observed in the T2D group, contrasting with the control (<i>P</i> < .05). Additionally, in ventral horn cells, AGEs emerged as an added pro-inflammatory factor.</p><p><strong>Conclusions: </strong>The KP is activated during diabetic neuropathy, and it displays divergent metabolic profiles in glia, motoneuron, and non-motoneuron, which differ from the controls. Their presence also evolves with time, indicating the dynamic nature of the process.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"18 ","pages":"11786469251372797"},"PeriodicalIF":4.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207922","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":"Molecular Insights Into the Interaction of Tryptophan Metabolites With Tryptophan and Indoleamine 2,3-Dioxygenases: Nitric Oxide a New Effector of Tryptophan 2,3-Dioxygenase and Their Roles in Infection.","authors":"Abdulla A-B Badawy, Shazia Dawood","doi":"10.1177/11786469251372339","DOIUrl":"10.1177/11786469251372339","url":null,"abstract":"<p><p>Feedback and other negative controls are important determinants of metabolic pathway activities. Other than inhibition of indoleamine 2,3-dioxygenase (IDO) by tryptophan (Trp) and nitric oxide (NO) and feedback inhibition of Trp 2,3-dioxygenase (TDO) by NAD(P)H, little is known of potential effects of Trp and kynurenine metabolites on the kynurenine (Kyn) pathway (KP). Whereas previous studies suggested that some Trp metabolites inhibit TDO activity in vitro, when administered in vivo to rats, inhibition is not always demonstrable, suggesting involvement of mitigating factors. To resolve this difference and provide indicators of likely interaction of Trp metabolites with TDO and IDO1, we performed molecular docking in silico of Trp and a range of its metabolites to these 2 KP enzymes. We found that Trp and many of its Kyn and 5-hydroxyindole metabolites docked to the active site of the TDO2 crystal structure, whereas no docking was observed with Kyn or kynurenic acid. Docking of NAD⁺(P⁺)H occurred at a different site, provisionally identified as the TDO allosteric site. By contrast, docking to IDO1 was limited to Trp, N'-formylkynurenine, 3-hydroxyanthranilic acid and picolinic acid. We conclude that bioinformatics can resolve controversial issues and identify amino acid residues at unexplored sites. The IDO1 effector nitric oxide (NO) docked to TDO as well as to IDO1. NO controls TDO2 and IDO1 activities in a dual fashion, through provision and limitation of the heme cofactor. We propose NO as a new TDO effector and discuss its role in control of TDO during acute inflammation. We propose TDO as an important player in the acute inflammatory responses in parallel with IDO1.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"18 ","pages":"11786469251372339"},"PeriodicalIF":4.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087710","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":"IBS May Have a Causal Effect on Increased Tryptophan Metabolites Levels: Insights from a Bidirectional Two-Sample Mendelian Randomization Study.","authors":"Peilin Cheng, Ruzhen Jia, Bingjie Jin, Feifei Zhou, Hongwei Xu, Ben Wang","doi":"10.1177/11786469251327399","DOIUrl":"10.1177/11786469251327399","url":null,"abstract":"<p><strong>Background: </strong>Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Tryptophan, an essential amino acid derived from dietary proteins, can be metabolized into various compounds by the gut microbiome. Emerging evidence suggests that tryptophan metabolites play a role in functional gastrointestinal disorders. However, the causal relationship between tryptophan metabolites and IBS remains to be fully elucidated.</p><p><strong>Objective: </strong>This study aims to evaluate the potential causal relationship between tryptophan metabolites and IBS using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Instrumental variables (IVs) were selected from summary data of genome-wide association studies (GWAS) for tryptophan and IBS. SNPs potentially influencing MR results were excluded through outlier detection using MR-PRESSO. Bidirectional two-sample MR analyses were conducted using the inverse-variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode methods. The MR-Egger intercept test was employed to assess pleiotropy and heterogeneity among IVs, with visualization of the MR results through scatter plots, funnel plots, and forest plots.</p><p><strong>Results: </strong>Genetically predicted tryptophan metabolites were not associated with the risk of IBS. In the reverse direction, genetically predicted IBS was associated with increased levels of tryptophan, serotonin, and kynurenine in the IVW analysis. Sensitivity and replication analyses confirmed these findings.</p><p><strong>Conclusion: </strong>The findings of this Mendelian randomization study suggest that IBS may lead to elevated levels of tryptophan, serotonin, and kynurenine. These results have important implications for understanding the interplay between tryptophan metabolism and IBS in clinical settings. Further research is warranted to explore the underlying mechanisms.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"18 ","pages":"11786469251327399"},"PeriodicalIF":2.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508826","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":"Activation of the IDO1-GCN2-ATF4-CHOP Pathway During the Massive Generation of Antibody-Secreting Cells in Dengue Patients Through Single-Cell Transcriptomics.","authors":"Jéssica C Nascimento, André N A Gonçalves, Karen T Akashi, Helder I Nakaya, Eduardo L V Silveira","doi":"10.1177/11786469251340237","DOIUrl":"10.1177/11786469251340237","url":null,"abstract":"<p><p>Dengue, a widespread mosquito-borne disease, annually afflicts millions globally, posing substantial mortality risks. Preceding disease defervescence, a marked and transient surge in antibody-secreting cell (ASC) frequency correlates with disease severity, paralleled by heightened tryptophan degradation. Investigating details of this process through single-cell transcriptomics from public repositories, our data pinpoint CD14+ monocytes as principal IDO1 and IDO2 expressors, implicating them, rather than B cells, in initiating tryptophan metabolism. Interestingly, naive B cells exhibit altered gene expression indicative of early impact by tryptophan deficiency before defervescence with a potential impact on the B cell fate. Dengue-induced ASCs upregulated GCN2, PERK, eIF2a, ATF4 genes as well as BIM and CASP-3. However, the high expression of anti-apoptotic genes (FKBP8 [a CHOP-regulated gene], BCL-XL, BCL-2, MCL-1) allows enhanced ASC survival. Proliferation and differentiation-related genes (eIF4EBP1, RRM2, and HIF1a) were also upregulated in ASCs. These findings untangle how Dengue modulates the host metabolism and B-cell responses, although further research is needed to fully understand their implications on disease progression.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"18 ","pages":"11786469251340237"},"PeriodicalIF":2.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508825","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":"Preoperative Peripheral Blood Serotonin and Kynurenine Levels Are Associated With Oncological Outcomes in Glioblastoma IDH-wt Patients.","authors":"Silvia Snider, Filippo Gagliardi, Pierfrancesco De Domenico, Stefano Comai, Antonella Bertazzo, Sofia Nasini, Benedetta Barzon, Angela Ruban, Francesca Roncelli, Pietro Mortini","doi":"10.1177/11786469241312475","DOIUrl":"10.1177/11786469241312475","url":null,"abstract":"<p><strong>Background: </strong>In recent years, there has been a growing interest in exploring the potential contribution of tryptophan (TRP) metabolism via the kynurenine (KP) and serotonin (SP) pathways in Glioblastoma (GBM) biology. This study aims to address the association between pre-operative peripheral blood levels of TRP, kynurenine (KYN), 5-hydroxy-tryptophan (5-HTP), and serotonin (5-HT) and relevant oncological outcomes in GBM IDH-wt patients.</p><p><strong>Methods: </strong>This is a single-center, retrospective clinical study. Serum from 62 adult patients undergoing maximal safe resection of newly diagnosed glioblastoma WHO-grade 4 IDH-wt (GBM) and n = 27 healthy controls were analyzed. The variables of interest were dichotomized via maximally selected rank statistics. Kaplan Meier and Cox multivariate regression analysis were conducted to explore the single contributions of these parameters in building a predictive model of overall survival (OS) and progression-free survival (PFS) in these patients.</p><p><strong>Results: </strong>The mean baseline serum levels of 5-HT, KYN, and 5-HTP were significantly lower in GBM when compared to n = 27 healthy individuals (<i>P</i> < .001). Patients with 5-HT <78 ng/mL had a median OS of 14.4 months compared to 22.5 months in patients with increased levels (<i>P</i> = .01). Shorter OS was observed in patients with KYN <18 ng/mL (9.8 vs 17.5 months, <i>P</i> = .002), KYN/TRP <2.55 (11.4 vs 17.1, <i>P</i> = .002), 5-HTP/TRP <0.89 (11.5 vs 17.6 months, <i>P</i> = .02), and 5-HT/TRP <5.78 (13.4 vs 19.1 months, <i>P</i> = .002) compared to patients with high levels. Shorter PFS in patients with 5-HT <78 ng/mL (<i>P</i> = .04), KYN <18 ng/mL (<i>P</i> = .02), 5-HT/TRP <5.78 (<i>P</i> = .001), KYN/TRP <2.55 (<i>P</i> = .005). Reduced KYN, 5-HTP, and 5-HT were independent predictors of poor OS.</p><p><strong>Conclusions: </strong>This study highlights an intriguing association between the degradation of TRP along the KP and SP and median survival times in GBM. Decreased KYN, 5-HTP, and 5-HT levels were associated with shorter OS.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"18 ","pages":"11786469241312475"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434274","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":"Relationship Between Psychological Stress Scores and Urinary 5-HT Levels Over Time Under Psychological Stress.","authors":"Tadayuki Iida, Yasuhiro Ito, Susumu Murayama, Yuki Yoshimaru, Asami Tatsumi","doi":"10.1177/11786469241297911","DOIUrl":"10.1177/11786469241297911","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers for psychological stress have been examined and the \"gut-microbiota-brain axis\" is currently attracting attention. An intervention study reported improvements in both the intestinal environment and psychological stress. However, the relationship between psychological stress scores and urinary 5-hydroxytryptamine (u-5-HT), produced by enterochromaffin cells in the intestinal tract, has not yet been investigated over time in healthy subjects under psychological stress. Therefore, the present study examined the relationship between subjective psychological stress (depression and anxiety) scores and u-5-HT levels over time in healthy women.</p><p><strong>Methods: </strong>The effects of the objective structured clinical examination (OSCE), considered to be a uniform source of psychological stress, on u-5-HT levels were assessed in 16 third-year female medical university students (21.3 ± 2.1 years old) in Japan with a normal menstrual cycle. A self-administered questionnaire consisting of Zung's Self-rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI) was used to evaluate subjective stress 1 month, 1 week, and 1 day before and 1 week after the OSCE. Pearson's product-momentum correlation coefficient was used to calculate the correlation coefficient between u-5-HT levels, STAI, and SDS for each examined period.</p><p><strong>Result: </strong>On the day before the OSCE, u-5-HT levels correlated with SDS and STAI (SDS: <i>r</i> = .524, <i>P</i> = .037, State-Anxiety: <i>r</i> = -.718, <i>P</i> = .002).</p><p><strong>Conclusion: </strong>A correlation was observed between subjective psychological stress scores and u-5-HT levels in healthy women under psychological stress.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 ","pages":"11786469241297911"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787393","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":"Baseline Inflammation but not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons With Multiple Sclerosis: Secondary Results From a Randomized Controlled Trial.","authors":"Marie Kupjetz, Nadine Patt, Niklas Joisten, Per Magne Ueland, Adrian McCann, Roman Gonzenbach, Jens Bansi, Philipp Zimmer","doi":"10.1177/11786469241284423","DOIUrl":"https://doi.org/10.1177/11786469241284423","url":null,"abstract":"<p><strong>Background: </strong>The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner.</p><p><strong>Objectives: </strong>To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes.</p><p><strong>Methods: </strong>For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS). Exercise-induced changes in the KP metabolite profile according to treatment and baseline systemic inflammation (neutrophil-to-lymphocyte ratio (NLR) <3.12 versus ⩾3.12) were investigated using covariance analyses.</p><p><strong>Results: </strong>Regardless of treatment, concentrations of tryptophan and most kynurenines decreased over time. Quinolinic acid concentration increased (<i>p</i> < .001). Participants with low and high NLR revealed differential exercise-induced changes in concentrations of kynurenines and NLR. The systemic inflammation markers neopterin (<i>p</i> = .015) and NLR (<i>p</i> < .001) decreased in the whole group and in participants with high NLR, respectively.</p><p><strong>Conclusions: </strong>Combined treatments including HIIT or MICT do not differentially modulate the KP metabolite profile, with both reducing concentrations of most kynurenines. Baseline systemic inflammation may impact exercise-induced changes in the KP metabolite profile and anti-inflammatory effects of exercise in pwMS.</p><p><strong>Trial registration: </strong>clinicaltrials.gov (identifier: NCT04356248).</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 ","pages":"11786469241284423"},"PeriodicalIF":2.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629900","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":"Erratum to 'Dietary Hesperidin Suppresses Lipopolysaccharide-Induced Inflammation in Male Mice'.","authors":"","doi":"10.1177/11786469241276659","DOIUrl":"https://doi.org/10.1177/11786469241276659","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/11786469221128697.].</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 ","pages":"11786469241276659"},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156312","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":"Investigations Towards Tryptophan Uptake and Transport Across an In Vitro Model of the Oral Mucosa Epithelium.","authors":"Grace C Lin, Julia Tevini, Lisa Mair, Heinz-Peter Friedl, Dietmar Fuchs, Thomas Felder, Johanna M Gostner, Winfried Neuhaus","doi":"10.1177/11786469241266312","DOIUrl":"10.1177/11786469241266312","url":null,"abstract":"<p><p>Tryptophan is an essential amino acid and plays an important role in several metabolic processes relevant for the human health. As the main metabolic pathway for tryptophan along the kynurenine axis is involved in inflammatory responses, changed metabolite levels can be used to monitor inflammatory diseases such as ulcerative colitis. As a progenitor of serotonin, altered tryptophan levels have been related to several neurogenerative diseases as well as depression or anxiety. While tryptophan concentrations are commonly evaluated in serum, a non-invasive detection approach using saliva might offer significant advantages, especially during long-term treatments of patients or elderly. In order to estimate whether active transport processes for tryptophan might contribute to a potential correlation between blood and saliva tryptophan concentrations, we investigated tryptophan's transport across an established oral mucosa in vitro model. Interestingly, treatment with tryptophan revealed a concentration dependent secretion of tryptophan and the presence of a saturable transporter while transport studies with deuterated tryptophan displayed increased permeability from the saliva to the blood compartment. Protein analysis demonstrated a distinct expression of L-type amino acid transporter 1 (LAT1), the major transporter for tryptophan, and exposure to inhibitors (2 -amino-2-norbornanecarboxylic acid (BCH), L-leucine) led to increased tryptophan levels on the saliva side. Additionally, exposure to tryptophan in equilibrium studies resulted in a regulation of LAT1 at the mRNA level. The data collected in this study suggest the participation of active transport mechanisms for tryptophan across the oral mucosa epithelium. Future studies should investigate the transport of tryptophan across salivary gland epithelia in order to enable a comprehensive understanding of tryptophan exchange at the blood-saliva barrier.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 ","pages":"11786469241266312"},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876308","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 Tryptophan Metabolite Indole-3-Propionic Acid Raises Kynurenic Acid Levels in the Rat Brain In Vivo.","authors":"Korrapati V Sathyasaikumar, Tonali Blanco-Ayala, Yiran Zheng, Lilly Schwieler, Sophie Erhardt, Maximilian Tufvesson-Alm, Burkhard Poeggeler, Robert Schwarcz","doi":"10.1177/11786469241262876","DOIUrl":"10.1177/11786469241262876","url":null,"abstract":"<p><p>Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects. Here, we evaluate an alternative and/or complementary mechanism, linking IPrA to kynurenic acid (KYNA), another neuroprotective tryptophan metabolite. Adult Sprague-Dawley rats received an oral dose of IPrA (200 mg/kg), and both IPrA and KYNA were measured in plasma and frontal cortex 90 minutes, 6 or 24 hours later. IPrA and KYNA levels increased after 90 minutes and 6 hours (brain IPrA: ~56- and ~7-fold; brain KYNA: ~4- and ~3-fold, respectively). In vivo microdialysis, performed in the medial prefrontal cortex and in the striatum, revealed increased KYNA levels (~2.5-fold) following the administration of IPrA (200 mg/kg, p.o), but IPrA failed to affect extracellular KYNA when applied locally. Finally, treatment with 100 or 350 mg IPrA, provided daily to the animals in the chow for a week, resulted in several-fold increases of IPrA and KYNA levels in both plasma and brain. These results suggest that exogenously supplied IPrA may provide a novel strategy to affect the function of KYNA in the mammalian brain.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 ","pages":"11786469241262876"},"PeriodicalIF":2.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443541","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}