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Mass spectrometry i...
Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA-induced dyskinesia
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- Fridjonsdottir, Elva (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri
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- Shariatgorji, Mohammadreza (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri
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- Vallianatou, Theodosia (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri
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- Odell, Luke R. (author)
- Uppsala universitet,Preparativ läkemedelskemi
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- Schembri, Luke S (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri
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- Svenningsson, Per (author)
- Karolinska Institutet
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- Fernagut, Pierre-Olivier (author)
- Univ Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France.;CNRS, Inst Malad Neurodegenerat, Bordeaux, France.;Univ Poitiers, INSERM, U0 1084, Lab Neurosci Expt & Clin, Poitiers, France.
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- Crossman, Alan R. (author)
- Univ Manchester, Manchester M13 9PL, Lancs, England.
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- Bezard, Erwan (author)
- Univ Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France.;CNRS, Inst Malad Neurodegenerat, Bordeaux, France.;Motac Neurosci, Manchester M15 6WE, Lancs, England.
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- Andrén, Per E., Professor, 1957- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri
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Shariatgorji, R (author)
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2021
- 2021
- English.
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:2
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Fridjonsdottir, ...
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Shariatgorji, Mo ...
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Nilsson, Anna
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Vallianatou, The ...
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Odell, Luke R.
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Schembri, Luke S
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Svenningsson, Pe ...
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Fernagut, Pierre ...
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Crossman, Alan R ...
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Bezard, Erwan
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Andrén, Per E., ...
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Shariatgorji, R
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Science Advances
- By the university
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Uppsala University
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Karolinska Institutet