2025
Parkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction
Wilson E, Umans J, Swarovski M, Minhas P, Mendiola J, Midttun Ø, Ulvik A, Shahid-Besanti M, Linortner P, Mhatre S, Wang Q, Channappa D, Corso N, Tian L, Fredericks C, Kerchner G, Plowey E, Cholerton B, Ueland P, Zabetian C, Gray N, Quinn J, Montine T, Sha S, Longo F, Wolk D, Chen-Plotkin A, Henderson V, Wyss-Coray T, Wagner A, Mormino E, Aghaeepour N, Poston K, Andreasson K. Parkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction. Npj Parkinson's Disease 2025, 11: 96. PMID: 40287426, PMCID: PMC12033312, DOI: 10.1038/s41531-025-00964-7.Peer-Reviewed Original ResearchCerebral spinal fluidKynurenine pathwayKynurenic acidQuinolinic acidSites of brainB-vitamin statusParkinson's diseasePD clinical featuresVitamin B6 deficiencyKP metabolitesClinical featuresClinical manifestationsCerebral inflammationClinical symptomsPatient subgroupsB6 deficiencySpinal fluidPathway dysfunctionKynurenineCompare bloodDiseaseInflammationVitaminIncreased QASoluble TREM2Elevated initial blood kynurenine is associated with increased odds of post-stroke infection Kynurenine and post-stroke infection
Dylla L, Reisz J, Poisson S, Herson P, Sansing L, Monte A. Elevated initial blood kynurenine is associated with increased odds of post-stroke infection Kynurenine and post-stroke infection. Journal Of Stroke And Cerebrovascular Diseases 2025, 34: 108268. PMID: 40015349, PMCID: PMC11970113, DOI: 10.1016/j.jstrokecerebrovasdis.2025.108268.Peer-Reviewed Original ResearchConceptsPost-stroke infectionsAssociated with increased oddsTryptophan metabolitesHistory of diabetes mellitusEnd stage renal diseaseNIH Stroke Scale scoreConcentrations of kynurenineAcute ischemic stroke patientsMultivariate logistic regressionStage renal diseaseStroke Scale scoreCirculating kynurenineIschemic stroke onsetIschemic stroke patientsKynurenine concentrationsConcentrations of tryptophanEmergency department admissionsKynurenic acidDiabetes mellitusMortality of ischemic strokeRenal diseaseTryptophan metabolismOdds ratioQuinolinic acidImmune response
2024
Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders
Li Y, Wang L, Huang J, Zhang P, Zhou Y, Tong J, Chen W, Gou M, Tian B, Li W, Luo X, Tian L, Hong L, Li C, Tan Y. Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders. Frontiers In Psychiatry 2024, 15: 1357293. PMID: 38680780, PMCID: PMC11046465, DOI: 10.3389/fpsyt.2024.1357293.Peer-Reviewed Original ResearchYoung Mania Rating ScaleBD-DAffective disordersBD-MDepressive symptomsHamilton Depression Scale-17 itemsRemission of depressive symptomsKynurenic acidMania Rating ScaleAcute manic episodeWeeks of antidepressantsRisk of MDDKynurenine pathwayAssociated with remissionAntipsychotic medicationDisrupt tryptophan metabolismManic symptomsDepressive disorderBD-D.Depressive episodeHAMD-17Mood stabilizersManic episodesBipolar disorderTryptophan pathway
2023
Role of the immune-kynurenine pathway in treatment-resistant schizophrenia
Chen W, Tian Y, Gou M, Wang L, Tong J, Zhou Y, Feng W, Li Y, Chen S, Liu Y, Wang Z, Pan S, Zhang P, Huang J, Yang X, Li C, Tian L, Hong L, Tan Y. Role of the immune-kynurenine pathway in treatment-resistant schizophrenia. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2023, 130: 110926. PMID: 38147973, DOI: 10.1016/j.pnpbp.2023.110926.Peer-Reviewed Original ResearchConceptsImmune-inflammatory response systemTreatment-resistant schizophreniaQUIN/KYNA ratioNon-TRS patientsHealthy controlsKynurenine pathwayKP metabolismKP activationKynurenic acidQuinolinic acidInflammation-related effectsPeripheral immune responseAnti-inflammatory cytokinesPro-inflammatory cytokinesBinary logistic regression analysisPathophysiology of schizophreniaLogistic regression analysisAge of onsetLower kynurenineKP metabolitesKYNA levelsIllness onsetPlasma levelsRisk factorsNMDA receptorsScientific Rationale for the Treatment of Cognitive Deficits from Long COVID
Zadeh A, Arnsten A, Wang M. Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID. Neurology International 2023, 15: 725-742. PMID: 37368329, PMCID: PMC10303664, DOI: 10.3390/neurolint15020045.Peer-Reviewed Original ResearchLong COVIDGlutamate carboxypeptidase IIKynurenic acidNicotinic alpha 7 receptorCognitive deficitsProduction of KYNACOVID-19 infectionDorsolateral prefrontal cortexAgonist guanfacineNeuronal firingCognitive symptomsAcetyl cysteineCognitive functionPrefrontal cortexScientific rationaleCarboxypeptidase IIPFC functionCOVIDDeficitsReceptorsTreatmentExecutive functioningNMDAGuanfacineNeurotransmission
2022
Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia
Arnsten AFT, Woo E, Yang S, Wang M, Datta D. Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia. Biological Psychiatry 2022, 92: 480-490. PMID: 35305820, PMCID: PMC9372235, DOI: 10.1016/j.biopsych.2022.02.003.Peer-Reviewed Original ResearchConceptsEnvironmental insultsMore superficial layersDorsolateral prefrontal cortexPrimate dlPFCInflammatory mechanismsInflammatory insultKynurenic acidNMDA receptorsReceptor neurotransmissionDendritic spinesLayer IIICAMP/PKAGlutamatergic synapsePrefrontal cortexInsultPotassium channelsNeurotransmissionCalcium signalingSynapsesGenetic insultsSuperficial layersSchizophreniaSpineCortexNeuromodulation
2021
Kynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolites
2015
The impact of electroconvulsive therapy on the tryptophan–kynurenine metabolic pathway
Guloksuz S, Arts B, Walter S, Drukker M, Rodriguez L, Myint A, Schwarz M, Ponds R, van Os J, Kenis G, Rutten B. The impact of electroconvulsive therapy on the tryptophan–kynurenine metabolic pathway. Brain Behavior And Immunity 2015, 48: 48-52. PMID: 25765557, DOI: 10.1016/j.bbi.2015.02.029.Peer-Reviewed Original ResearchConceptsTrp-Kyn pathwayHamilton Depression Rating Scale-17 itemsElectroconvulsive therapyBeck Depression InventoryMechanism of actionKynurenic acidTrp-KynKyn/Trp ratioKYNA/KYN ratioTryptophan-kynurenine metabolic pathwayLast ECT sessionBilateral electroconvulsive therapyKyn/TrpTreatment of depressionMultilevel linear regression analysesKYN metabolitesECT sessionsAntidepressant effectsECT responseBipolar depressionECT treatmentTrp ratioNeuroprotective propertiesKynurenine pathwayNeurotoxic processes
2013
Relationship between postprandial metabolomics and colon motility in children with constipation
Rodriguez L, Roberts LD, LaRosa J, Heinz N, Gerszten R, Nurko S, Goldstein AM. Relationship between postprandial metabolomics and colon motility in children with constipation. Neurogastroenterology & Motility 2013, 25: 420-e299. PMID: 23421516, PMCID: PMC3877617, DOI: 10.1111/nmo.12086.Peer-Reviewed Original ResearchConceptsTreatment of constipationColonic motilityMotility indexMotility patternsNormal postprandial increasePostprandial motility patternCohort of childrenPostprandial metabolic changesSignificant metabolite changesColon manometryColon motilityConstipated childrenProspective studyStandardized mealKynurenic acidMeal challengePostprandial increasePostprandial changesMultiple time pointsConstipationLipid metabolitesPotential metabolic targetsAbstractTextSpecific metabolitesMetabolic changes
2006
Effects of intertrigeminal region NMDA and non-NMDA receptors on respiratory responses in rats
Radulovacki M, Stoiljkovic M, Saponjic J, Carley D. Effects of intertrigeminal region NMDA and non-NMDA receptors on respiratory responses in rats. Respiratory Physiology & Neurobiology 2006, 156: 40-46. PMID: 16934539, DOI: 10.1016/j.resp.2006.07.005.Peer-Reviewed Original ResearchConceptsNon-NMDA receptorsIntertrigeminal regionNMDA receptorsReflex apneaNonspecific glutamate receptor antagonist kynurenic acidGlutamate receptor antagonist kynurenic acidSpecific NMDA receptor antagonistRespiratory responsesAntagonist kynurenic acidVentral respiratory groupMicroinjection of glutamateNMDA receptor antagonistSleep-related apneaLong-term potentiationFunctional NMDA receptorsImmediate apneaVagal reflexGlutamate injectionRespiratory groupRespiratory disturbancesKynurenic acidReceptor antagonistSelective blockadeApneaLateral pons
2001
Microtubule-associated protein 2 phosphorylation is decreased in the human epileptic temporal lobe cortex
Sánchez C, Arellano J, Rodríguez-Sánchez P, Avila J, DeFelipe J, Díez-Guerra F. Microtubule-associated protein 2 phosphorylation is decreased in the human epileptic temporal lobe cortex. Neuroscience 2001, 107: 25-33. PMID: 11744243, DOI: 10.1016/s0306-4522(01)00338-4.Peer-Reviewed Original ResearchConceptsEpileptic patientsMAP2 phosphorylationEpileptiform activityKynurenic acidTemporal lobe epileptic patientsNeuronal cytoskeletonSeizure-like activityTemporal lobe cortexNeuronal cell deathRat hippocampal neuronsProtein 2 phosphorylationNeuronal damageSeizure activityGlutamate receptorsHippocampal neuronsNeuronal activityBiopsy samplesSynaptic plasticityPatientsElectrocorticogram activityNeuronal processesExperimental modelAbnormal patternsImmunocytochemical analysisPhosphorylated epitopes
2000
Nicotine‐induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid
Erhardt S, Hajos M, Lindberg A, Engberg G. Nicotine‐induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid. Synapse 2000, 37: 104-108. PMID: 10881031, DOI: 10.1002/1098-2396(200008)37:2<104::aid-syn4>3.0.co;2-l.Peer-Reviewed Original ResearchConceptsEndogenous brain kynurenic acidCentral noradrenergic neuronsBrain kynurenic acidEndogenous kynurenic acidKynurenic acidNoradrenergic neuronsLocus coeruleusLevels of KYNAEndogenous glutamate receptor antagonistBrain KYNA levelsNicotine-induced excitationGlutamate receptor antagonistsLocus coeruleus neuronsAction of nicotineRelease of glutamatePresent electrophysiological studyGlutamatergic responsesKYNA levelsLC neuronsCoeruleus neuronsPeripheral originReceptor antagonistAnesthetized ratsElectrophysiological studiesLow doses
1995
Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: Relation to clinical and biochemical variable
Demitrack M, Heyes M, Altemus M, Pigott T, Gold P. Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: Relation to clinical and biochemical variable. Biological Psychiatry 1995, 37: 512-520. PMID: 7542489, DOI: 10.1016/0006-3223(94)00173-z.Peer-Reviewed Original ResearchConceptsCerebrospinal fluid levelsKynurenic acidKynurenine pathwayQuinolinic acidFluid levelsBody weightAnorexia nervosaMedication-free female patientsN-methyl-D-aspartate receptor agonistExcitatory amino acid receptorsL-kynurenineNormal weight bulimia nervosaAcid levelsQuinolinic acid levelsAmino acid receptorsKynurenic acid levelsNormal body weightNormal-weight femalesL-tryptophanEating Disorder PatientsUnderweight anorecticsUnderweight phaseEating-disordered patientsNutritional recoveryFemale patients
1991
Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration
Rasmussen K, Krystal J, Aghajanian G. Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration. Psychopharmacology 1991, 105: 508-512. PMID: 1771218, DOI: 10.1007/bf02244371.Peer-Reviewed Original ResearchConceptsAcid administrationKynurenic acidSubcutaneous administrationPeripheral excitatory amino acid receptorsExcitatory amino acid antagonist kynurenic acidExcitatory amino acid receptorsAntagonist kynurenic acidExcitatory amino acidsAmino acid receptorsLocus coeruleus neuronsMorphine-dependent ratsBlood-brain barrierSingle-unit recordingsMorphine withdrawalCoeruleus neuronsAntagonist treatmentAbstinence symptomsOpiate withdrawalUnit recordingsAnesthetized animalsAcid receptorsBehavioral signsAdministrationDifferential effectsWithdrawal
1990
Kynurenic acid blocks chemogenic nociception
Hajós M, Engberg G. Kynurenic acid blocks chemogenic nociception. Journal Of Pharmacy And Pharmacology 1990, 42: 373-374. PMID: 1976793, DOI: 10.1111/j.2042-7158.1990.tb05434.x.Peer-Reviewed Original Research
1989
The Effect of L-Tryptophan on Daytime Sleep Latency in Normals: Correlation with Blood Levels
George C, Millar T, Hanly P, Kryger M. The Effect of L-Tryptophan on Daytime Sleep Latency in Normals: Correlation with Blood Levels. Sleep 1989, 12: 345-353. PMID: 2669092, DOI: 10.1093/sleep/12.4.345.Peer-Reviewed Original ResearchConceptsSleep latencyBlood levelsRandom double-blind fashionRapid eye movement (REM) sleepDaytime sleep latencyL-tryptophan's effectsDouble-blind fashionEye movement sleepL-tryptophanSlow-wave sleepL-tryptophan levelsObjective sleepiness measuresKynurenic acidMovement sleepHealthy volunteersWave sleepDrug conditionsSeparate daysSleepSleepiness measuresPlaceboSignificant correlationEssential amino acidsDoseUrine
1987
Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus
Poolos N, Mauk M, Kocsis J. Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus. Journal Of Neurophysiology 1987, 58: 404-416. PMID: 3655875, DOI: 10.1152/jn.1987.58.2.404.Peer-Reviewed Original ResearchConceptsEnd of stimulationConduction velocityRepetitive stimulationCA1 afferentsStratum radiatumCA1 regionPostsynaptic elementsPostsynaptic activityBiphasic changeRat hippocampal slice preparationCompound action potentialHippocampal slice preparationCharacteristic field potentialHigher stimulation frequenciesPostsynaptic modulationPresynaptic volleyKynurenic acidPyramidal cellsSlice preparationPresynaptic axonsPresynaptic excitabilitySynaptic transmissionConduction blockIon-sensitive microelectrodesPostsynaptic activation
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