Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia. Issue 5 (11th July 2017)

• Record Type: Journal Article
• Authors: Havelund, Jesper F.; Andersen, Andreas D.; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H.H.; Stenager, Egon; Færgeman, Nils J.; Gramsbergen, Jan Bert
• Is Part Of: Journal of neurochemistry. Volume 142:Issue 5(2017)
• Page Start: 756
• Page End: 766
• Publication Date: 2017-07-11
• Subjects: 3‐hydroxykynurenine -- biomarkers -- kynurenic acid -- levodopa -- metabolomics -- tryptophan; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14104
• Languages: English
• ISSNs: 0022-3042

Abstract

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. Abstract : We observed marked changes in kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients with L‐DOPA‐induced dyskinesia as compared to controls or non‐dyskinetic Parkinson's patients. We suggest that an increased ratio of 3‐hydroxykynurenine/kynurenic acid in plasma may serve as a biomarker and may play a role in the pathopysiology of L‐DOPA‐induced dyskinesia.