Mass spectrometry imaging identifies abnormally elevated brain l -DOPA levels and extrastriatal monoaminergic dysregulation in l -DOPA–induced dyskinesia
Open Access
- 8 January 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (2), eabe5948
- https://doi.org/10.1126/sciadv.abe5948
Abstract
L-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.Funding Information
- FP7 People: Marie-Curie Actions (607517)
- Agence Nationale de la Recherche (ANR-07-MNP TRAFINLID)
- Agence Nationale de la Recherche (ANR-08-MNP-018 MCHPRIMAPARK)
- Swedish Foundation for Strategic Research (RIF14-0078)
- Hjärnfonden (FO2018-0292)
- Vetenskapsrådet (2018–03320)
- Vetenskapsrådet (2018–05501)
- Uppsala Universitet
- Science for Life Laboratory
- Fédération pour la Recherche sur le Cerveau
- Biothèque Primate — CNRS Life Sciences Department
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