Monitoring of kynurenine pathway metabolites, neurotransmitters and their metabolites in blood plasma and brain tissue of individuals with latent toxoplasmosis

Vondroušová, Jana; Mikoška, Miloš; Syslová, Kamila; Böhmová, Adéla; Tejkalová, H.; Vacek, Lukas; Kodym, Petr; Krsek, Daniel; Horáček, J

doi:10.1016/j.jpba.2019.03.039

Cited by 8 publications

(10 citation statements)

References 21 publications

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“…23,24 However, the neurobiological relevance of this route lies mainly in that there is evidence that some of its intermediate metabolites have redox and neuroactive properties, modulating glutamatergic, cholinergic, and dopaminergic neurotransmission. 25 Previous meta analytic studies have shown consistent changes in serum levels of KP metabolites: a reduction of serum tryptophan, KYNA, and L-Kyn and an increase of QUIN and 3HK in patients with major depression. 9,10,26,27 However, the relationship of serum kynurenines with anxious-depressive symptoms in patients with stroke has been comparatively little studied.…”

Section: Discussionmentioning

confidence: 86%

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study

Carrillo‐Mora

Cruz

Estrada-Cortés

et al. 2020

Neurorehabil Neural Repair

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Background Poststroke depression (PSD) is related to adverse functional and cognitive prognosis in stroke patients. The participation of kynurenine pathway metabolites in depression has been previously proposed; however, there are few studies on its role in PSD and disability in stroke. Objective To investigate if there is a correlation between serum kynurenines levels with poststroke anxiety and depression symptoms and disability scales. Methods A cross-sectional case-control study was conducted in patients with first stroke, of >1 month and <1 year of evolution, with no history of previous psychiatric or neurological disorders; the Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA), functional evaluations (Barthel index, Functional Independence Measure [FIM]) were applied and serum kynurenines (Kyns) were determined. Results Sixty patients were included; significant depressive symptoms were found in 63% of the cases; a significant and positive correlation was obtained between levels of 3-hydroxykynurenine (3-HK) with HADS-T ( r = 0.30, P = .025) and HADS-D ( r = 0.28, P = .039). Depressed patients showed significantly higher levels of 3HK ( P = .048) and KYNA ( P = .0271) than nondepressed patients; the 3HK levels were inversely correlated with functional scales: Barthel index ( r = −0.31, P = .02), FIM ( r = −0.40, P = .01); in addition, serum 3HK levels were significantly higher in patients with poor sleep quality ( P = .0190). Conclusions Serum Kyns show correlation with the presence and severity of depressive symptoms and with the disability and sleep quality. Kyns may be a potential marker of depression risk and disability in stroke in future.

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Section: Discussionmentioning

confidence: 86%

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study

Carrillo‐Mora

Cruz

Estrada-Cortés

et al. 2020

Neurorehabil Neural Repair

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“…Tryptophan is an essential amino acid known for its influence on immunological and neurological activity, being a precursor for the synthesis of proteins and nicotinamide adenine dinucleotide (NAD), as well as nicotinic acid and serotonin [ 14 ]. Moreover, a number of its metabolites may pass the blood–brain barrier, having neuroactive properties on the brain physiology connected to behavioral changes [ 15 , 16 ]. Tryptophan metabolism consists mainly of two competing major metabolic pathways: the kynurenine pathway that converts approximately 95% of tryptophan and the serotonin pathway that metabolizes 5% of the amino acid.…”

Section: Discussionmentioning

confidence: 99%

“…Kynurenine may be further metabolized along three neurotoxic branches, with the consequent formation of 3-hydroxy-L-kynurenine, kynurenic acid and anthranilic acid. In general, it has been reported that metabolites in the kynurenine pathway take part in different pathophysiological processes, including neurodegenerative and neurological diseases and even psychiatric disorders such as schizophrenia or depression [16]. Several studies have described the effects of THC on tryptophan conversion and the association with behavioral and neurological changes.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

et al. 2021

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The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0–24 h). Ultra-high-performance liquid chromatography–tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.

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“…Supernatants after centrifugation were neutralized with 1vol of 1mol/L phosphate buffer (pH 7.3) before analysis HPLC-FD, HPLC-UV Too et al (2016) Plasma, brain Plasmatic proteins were removed by acetonitrile (0.2 mL ACN /0.1 mL plasma). Supernatants from the homogenate were further filtered through nylon filters; brain tissues were homogenized and sonicated in ACN, hydrochloric acid (100 mM) and EDTA (27 mM solution) mixture at 5:4:1 (v/v/v) ratio, followed by supernatants filtration HPLC-ESI-MS/MS Vondrousova et al (2019) Forebrain, liver Frozen tissues were homogenized (1:20, w/v) in an aqueous solution containing 0.1% ascorbic acid and internal standards. Proteins were denatured using acetone followed by centrifugation.…”

Section: Discussionmentioning

confidence: 99%

Quantification of IDO1 enzyme activity in normal and malignant tissues

Zhai

Ladomersky

Bell

et al. 2019

Methods in Enzymology

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Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting reaction of Ltryptophan (Trp) conversion into L-kynurenine (Kyn). The depletion of Trp, and the accumulation of Kyn have been proposed as mechanisms that contribute to the suppression of the immune response-primarily evidenced by in vitro study. IDO1 is therefore considered to be an immunosuppressive modulator and quantification of IDO1 metabolism may be critical to understanding its role in select immunopathologies, including autoimmune-and oncologicalconditions, as well as for determining the potency of IDO1 enzyme inhibitors. Because tryptophan 2,3-dioxygenase (TDO), and to a significantly lesser extent, IDO2, also catabolize Trp into Kyn, it's important to differentiate the contribution of each enzyme to Trp catabolism and Kyn generation. Moreover, a great variety of detection methods have been developed for the quantification of Trp metabolites, but choosing the suitable protocol remains challenging. Here, we review the differential expression of IDO1/TDO/IDO2 in normal and malignant tissues, followed by a comprehensive analysis of methodologies for quantifying Trp and Kyn in vitro and in vivo, with an emphasis on the advantages/disadvantages for each application.

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Monitoring of kynurenine pathway metabolites, neurotransmitters and their metabolites in blood plasma and brain tissue of individuals with latent toxoplasmosis

Cited by 8 publications

References 21 publications

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

Quantification of IDO1 enzyme activity in normal and malignant tissues

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