| Autor: |
Havelund, Jesper F., Andersen, Andreas D., Binzer, Michael, Blaabjerg, Morten, Heegaard, Niels H.H., Stenager, Egon, Færgeman, Nils J., Gramsbergen, Jan Bert |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Sep2017, Vol. 142 Issue 5, p756-766, 11p |
| Abstrakt: |
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 ( UDys RS). 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 FROM AUTHOR] |
| Databáze: |
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