Abstract
The present study was performed to examine if catechol oxidation is higher in brains from patients with Parkinson’s disease compared to age-matched controls, and if catechol oxidation increases with age. Brain tissue from Parkinson patients and age-matched controls was examined for oxidation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) to corresponding quinones, by measurement of 5-S-cysteinyl-dopamine, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA. The cysteinyl catechols are assumed to be biomarkers for DA, DOPAC and DOPA autoxidation and part of the biosynthetic pathway of neuromelanin. The concentrations of the 5-S-cysteinyl catechols were lower, whereas the 5-S-cysteinyl-DA/DA and 5-S-cysteinyl-DOPAC/DOPAC ratios tended to be higher in the Parkinson group compared to controls, which was interpreted as a higher degree of oxidation. High 5-S-cysteinyl-DA/DA ratios were found in the substantia nigra of a sub-population of the Parkinson group. Based on 5-S-cysteinyl-DA/DA ratios, dopamine oxidation was found to increase statistically significantly with age in the caudate nucleus, and non-significantly in the substantia nigra. In conclusion, the occurrence of 5-S-cysteinyl-DA, 5-S-cysteinyl-DOPAC and 5-S-cysteinyl-DOPA was demonstrated in dopaminergic brain areas of humans, a tendency for higher oxidation of DA in the Parkinson group compared to controls was observed as well as a statistically significant increase in DA oxidation with age. Possibly, autoxidation of DA and other catechols are involved in both normal and pathological ageing of the brain. This study confirms one earlier but small study, as well as complements one study on non-PD cases and one study on both PD cases and controls on NM bound or integrated markers or catechols.
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Data Availability
Data is available to support the present publication. However, since the final analyses were performed in 1992, not all detailed analyses data are available any longer.
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Acknowledgements
The author wishes to thank Dr. Arvid Carlsson for his major role in planning, critically analysing, discussing, and concluding the results of the current study. The author also wishes to thank Dr. Evald Rosengren for preparing the 5-S-cysteinyl adducts of DA, DOPAC and DOPA. The excellent technical assistance of Mrs. Ingrid Bergh is gratefully acknowledged. We also wish to acknowledge Dr. David Dahlgren, Department of Pharmaceutical Biosciences, Uppsala University for preparing figures and reviewing the manuscript and Prof. Torgny Fornstedt, Department of Engineering and Chemical Sciences, Karlstad, for reviewing the updated manuscript. This study was supported by grants from the Swedish Medical Research Council (No. 155), the Upjohn Company, Adlerbertska forskningsfonden, Anna Ahrenbergs fondGun och Bertil Stohnes Stiftelse, Loo och Hans Ostermans fond för medicinsk forskning, Margnus Bergvalls stiftelse, Neurologiskt handikappades förbund, Stiftelsen Clas Groschisnkys Minnesfond, Stiftelsen för Gamla Trotjännarinnor, Stiftelsen Handlanden Hjalmar Svenssons forskningsfond, Stiftelsen Sigurd och Elsa Goljes Minne, Svenska Läkaresällskapet, Svenska Sällskapet för Medicinsk forskning, Wilhelm och Martina Lundgrens vetenskapsfond, Åhlén-stiftelsen, and the Medical Faculty, University of Göteborg.
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Fornstedt Wallin, B. Oxidation of dopamine and related catechols in dopaminergic brain regions in Parkinson’s disease and during ageing in non-Parkinsonian subjects. J Neural Transm 131, 213–228 (2024). https://doi.org/10.1007/s00702-023-02718-2
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DOI: https://doi.org/10.1007/s00702-023-02718-2