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

Jesper F Havelund, Andreas Dammann Andersen, Michael Binzer, Morten Blaabjerg, Niels H H Heegaard, Egon Stenager, Nils J Faergeman, Jan Bert Gramsbergen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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. (Figure presented.).

Original languageEnglish
JournalJournal of Neurochemistry
Volume142
Issue number5
Pages (from-to)756–766
ISSN0022-3042
DOIs
Publication statusPublished - Sep 2017

Keywords

  • Journal Article
  • 3-hydroxykynurenine
  • levodopa
  • metabolomics
  • biomarkers
  • kynurenic acid
  • tryptophan
  • Single-Blind Method
  • Dyskinesia, Drug-Induced/blood
  • Antiparkinson Agents/adverse effects
  • Humans
  • Middle Aged
  • Levodopa/adverse effects
  • Male
  • Signal Transduction/drug effects
  • Parkinson Disease/blood
  • Denmark/epidemiology
  • Adult
  • Biomarkers/blood
  • Female
  • Aged
  • Kynurenine/blood

Fingerprint

Dive into the research topics of 'Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia'. Together they form a unique fingerprint.

Cite this