Central kynurenine pathway shift with age in women

Bie, Josien de; Guest, Jade; Guillemin, Gilles J.; Grant, Ross

doi:10.1111/jnc.13496

Cited by 69 publications

(55 citation statements)

References 24 publications

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“…In our cohort, aging was most strongly associated with increased serum and CSF concentrations of Kyn, KA, and QA. These results are in accordance with previous studies (Gramsbergen et al 1992;Heyes et al 1992;Braidy et al 2011;Theofylaktopoulou et al 2013;de Bie et al 2016;Giil et al 2017) and suggest that the Kyn pathway is activated during aging in mammals. There is strong evidence that indicates that aging is associated with a low-grade inflammatory phenotype (Salminen et al 2012).…”

Section: Discussionsupporting

confidence: 93%

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Sorgdrager

Vermeiren

Faassen

et al. 2019

Journal of Neurochemistry

106

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The kynurenine (Kyn) pathway, which regulates neuroinflammation and N‐methyl‐d‐aspartate receptor activation, is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Age‐related changes in Kyn metabolism and altered cerebral Kyn uptake along large neutral amino acid transporters, could contribute to these diseases. To gain further insight into the role and prognostic potential of the Kyn pathway in PD and AD, we investigated systemic and cerebral Kyn metabolite production and estimations of their transporter‐mediated uptake in the brain. Kyn metabolites and large neutral amino acids were retrospectively measured in serum and cerebrospinal fluid (CSF) of clinically well‐characterized PD patients (n = 33), AD patients (n = 33), and age‐matched controls (n = 39) using solid‐phase extraction‐liquid chromatographic‐tandem mass spectrometry. Aging was disease independently associated with increased Kyn, kynurenic acid and quinolinic acid in serum and CSF. Concentrations of kynurenic acid were reduced in CSF of PD and AD patients (p = 0.001; p = 0.002) but estimations of Kyn brain uptake did not differ between diseased and controls. Furthermore, serum Kyn and quinolinic acid levels strongly correlated with their respective content in CSF and Kyn in serum negatively correlated with AD disease severity (p = 0.002). Kyn metabolites accumulated with aging in serum and CSF similarly in PD patients, AD patients, and control subjects. In contrast, kynurenic acid was strongly reduced in CSF of PD and AD patients. Differential transporter‐mediated Kyn uptake is unlikely to majorly contribute to these cerebral Kyn pathway disturbances. We hypothesize that the combination of age‐ and disease‐specific changes in cerebral Kyn pathway activity could contribute to reduced neurogenesis and increased excitotoxicity in neurodegenerative disease.

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Section: Discussionsupporting

confidence: 93%

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Sorgdrager

Vermeiren

Faassen

et al. 2019

Journal of Neurochemistry

106

View full text Add to dashboard Cite

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“…The major findings are the significant decreases of AA and KYNA in plasma of dyskinetic (PD-LID) versus non-dyskinetic L-DOPA-treated PD patients (PD-L) and a significant increase of the 3-HK/KYNA ratio in plasma of PD-LID versus controls and PD-N. The presented quantitative LC-MS analysis of tryptophan and kynurenine metabolites in human plasma and CSF showed absolute levels of the measured analytes in agreement with those reported previously for plasma (Widner et al 2002;Forrest et al 2010;Savitz et al 2015) and CSF (Olsson et al 2012;Kegel et al 2014;de Bie et al 2016;Sellgren et al 2016).…”

Section: Discussionsupporting

confidence: 88%

Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia

Havelund

Andersen

Binzer

et al. 2017

Journal of Neurochemistry

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L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia.

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“…These findings are in line with current research and are possibly explained by chronic inflammation [41,42].…”

Section: Discussionsupporting

confidence: 81%

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier

Ottiger

Vögeli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). Methods: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. Results: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a

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Central kynurenine pathway shift with age in women

Cited by 69 publications

References 24 publications

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

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