Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment among HIV-infected Individuals

Keegan, Michael R; Chittiprol, Seetharamaiah; Letendre, Scott; Winston, Alan; Fuchs, Dietmar; Boasso, Adriano; Iudicello, Jennifer E.; Ellis, Ronald J.

doi:10.4137/ijtr.s36464

Cited by 50 publications

(44 citation statements)

References 78 publications

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“…The results of the measurements of the metabolites of interest from the assessed biological matrices (mouse plasma and brain, human plasma and CSF) with the developed and validated method are summarized in Table 4. All the reported data in the current study are in line with those obtained from the scientific literature [9,10,15,16,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Section: Application Of the Developed Methods On Different Biological supporting

confidence: 83%

HPLC method for the assessment of tryptophan metabolism utilizing separate internal standard for each detector

Cseh

Veres

Szentirmai

et al. 2019

Analytical Biochemistry

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Abbreviations: 3NLT 3-nitro-L-tyrosine, 5-HT serotonin, ACN acetonitrile, CS(s) calibration standard(s), CSF cerebrospinal fluid, FLD fluorescence detector, HCA 4-hydroxyquinazoline-2carboxylic acid, HPLC high-performance liquid chromatography, IS(s) internal standard(s), IQR interquartile range, KP kynurenine pathway, KYN kynurenine, KYNA kynurenic acid, LOD limit of detection, LOQ limit of quantification, SD standard deviation, PCA perchloric acid, TRP tryptophan, UVD UV detector, ZnAc zinc acetate, WS working solution, ww wet weight 2 AbstractThe development of a validated method, applicable for the measurement of tryptophan (TRP) and serotonin (5-HT), and that of the neuroprotective branch of the kynurenine pathway from several different biological matrices, including mouse brain, is described. Following the spectral analysis of the metabolites, they were quantified with reversed-phase high-performance liquid chromatography (HPLC), using separate internal standards (ISs) for UV (3-nitro-L-tyrosine) and fluorescent (the newly utilized 4-hydroxyquinazoline-2-carboxylic acid) detectors. With regard to validation parameters, selectivity, linearity, limit of detection, limit of quantification, precision and recovery were determined. Although the linearity ranges were different for the assessed matrices, the correlation coefficient was > 0.999 in each case. Furthermore, good intraand inter-day precision values were obtained with coefficient of variation < 5%, and bias < 6.5% (except the 5-HT level in brain samples), respectively. The recoveries varied between 82.5% and 116%. The currently developed methods yield opportunities for the assessment of concentration changes in the TRP metabolism from a wide range of biological matrices, therefore they may well be utilized in future clinical and preclinical studies, especially in view that so many metabolites with the application of ISs have not been detected from mouse brain with such a simple HPLC method before.

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Section: Application Of the Developed Methods On Different Biological supporting

confidence: 83%

HPLC method for the assessment of tryptophan metabolism utilizing separate internal standard for each detector

Cseh

Veres

Szentirmai

et al. 2019

Analytical Biochemistry

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“…Tyrosine, phenylalanine, and tryptophan have been widely reported in the study of depression models (Eskelund et al, 2016;Keegan et al, 2016). Phenylalanine is an essential amino acid, and its metabolic process is to produce tyrosine with PAH in the liver.…”

Section: Amino Acid Metabolism and Synthesis Of Neurotransmittersmentioning

confidence: 99%

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Chang

et al. 2020

Front. Pharmacol.

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Background: Depression is a long-term complex psychiatric disorder, and its etiology remains largely unknown. Valeriana jatamansi Jones ex Roxb (V. jatamansi) is used in the clinic for the treatment of depression, but there are insufficient reports of its antidepressive mechanisms and a poor understanding of its endogenous substance-related metabolism. The objective of this study was to identify biomarkers related to depression in serum samples and evaluate the antidepressive effects of the iridoid-rich fraction of V. jatamansi (IRFV) in a chronic unpredictable mild stress (CUMS) mouse model. Methods: Here, CUMS was used to establish a mouse model of depression. Behavioral and biochemical indicators were investigated to evaluate the pharmacodynamic effects. A comprehensive serum metabolomics study by nuclear magnetic resonance (NMR) approach was applied to investigate the pharmacological mechanism of IRFV in CUMS mouse. Subsequently, we used multivariate statistical analysis to identify metabolic markers, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), to distinguish between the CUMS mouse and the control group. Results: After IRFV treatment, the immobility time, sucrose preference, and monoamine neurotransmitter were improved. PCA scores showed clear differences in metabolism between the CUMS group and control group. The PLS-DA or OPLS-DA model exhibited 26 metabolites as biomarkers to distinguish between the CUMS mice and the control mouse. Moreover, IRFV could significantly return 21 metabolites to normal levels. Conclusion: The results confirmed that IRFV exerted an antidepressive effect by regulating multiple metabolic pathways, including the tricarboxylic acid cycle, the synthesis of neurotransmitters, and amino acid metabolism. These findings provide insights into the antidepressive mechanisms of IRFV.

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“…The increase in the indolamine-2,3-dioxygenase (IDO), the tryptophan-metabolizing enzyme, has been associated with immunological and inflammatory disorders, at least in animal models (Wirthgen et al 2016 ). Actually, tryptophan levels in urine can help researchers to highlight the relationship between this amino acid and its relationship with catabolites such as kynurenine with neurological and cognitive disorders associated with immune-related pathology (Gabbay et al 2010 ; Keegan et al 2016 ). The relationship between tryptophan and neurological disorders may be explained by the evidence that this amino acid is a known precursor of fundamental neuromodulators, and can even explain the recent evidence about its therapeutical use in neuroscience, despite the existence of controversial results (Wang et al 2016 ; Nagashima et al 2017 ; Silva et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Tryptophan status in autism spectrum disorder and the influence of supplementation on its level

et al. 2017

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Recent reports show that the worldwide incidence of autism spectrum disorder (ASD) is dramatically increasing, although ASD etiology and pathogenesis are still far to be fully elucidated. Some dietary-derived essential compounds, such as the amino acid tryptophan, appear to be impaired in patients with ASD. Tryptophan (Trp) plays a significant role in the human organism and serves as a precursor for a wide range of bioactive compounds, including major neurotransmitters. Research indicates that tryptophan might be deficient in subjects with ASD. Deficiency in the tryptophan level can be retrieved by investigating Trp levels or its major metabolite kynurenine in urines. The purpose of the present study is to quantify tryptophan content in urine samples (n = 236) of ASD patients, who underwent a supplemented dietary panel with B vitamins and magnesium, compared to controls (without this diet regimen). The samples were analyzed with gas chromatography-mass spectrometry. Additionally, the correlation between body mass index (BMI) and the level of this amino acid in urine was accomplished. Basic parameters of urine samples were also evaluated. Statistical evaluations in the concentration of tryptophan in ASD patients with different severity of symptoms were reported. A significant difference in tryptophan levels in all groups was observed.Supplementation with B vitamins and magnesium has an influence on the Trp concentration. Furthermore, no correlation between BMI and tryptophan levels was found. These results assess that the Trp level in ASD subjects is critical and that intake of B vitamins and magnesium with diet might influence its metabolic homeostasis.

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Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment among HIV-infected Individuals

Cited by 50 publications

References 78 publications

HPLC method for the assessment of tryptophan metabolism utilizing separate internal standard for each detector

HPLC method for the assessment of tryptophan metabolism utilizing separate internal standard for each detector

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Tryptophan status in autism spectrum disorder and the influence of supplementation on its level

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