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Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA-induced dyskinesia

Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA-induced dyskinesia

DownLoad

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.

Reference

Fridjonsdottir, E., Shariatgorji, R., Nilsson, A., Vallianatou, T., Odell, L. R., Schembri, L. S., ... & Andrén, P. E. (2021). Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA–induced dyskinesia. Science Advances, 7(2), eabe5948.


For Research Use Only. Not For Clinical Use.
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