Open AccessMass spectrometry imaging identifies abnormally elevated brain l -DOPA levels and extrastriatal monoaminergic dysregulation in l -DOPA–induced dyskinesia
Author(s) -
Elva Fridjonsdottir,
Mohammadreza Shariatgorji,
Anilsson,
Theodosia Vallianatou,
Luke R. Odell,
Luke S. Schembri,
Per Svenningsson,
PierreOlivier Fernagut,
Alan R. Crossman,
Erwan Bézard,
Per E. Andrén
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abe5948
Subject(s) - monoaminergic , dopamine , striatum , stria terminalis , dyskinesia , neuroscience , hippocampus , amygdala , parkinson's disease , medicine , endocrinology , chemistry , biology , disease , serotonin , receptor
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.