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  • Fridjonsdottir, ElvaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri (author)

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

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • American Association for the Advancement of Science (AAAS),2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-435739
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-435739URI
  • https://doi.org/10.1126/sciadv.abe5948DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:145690296URI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Shariatgorji, MohammadrezaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri(Swepub:uu)mohsh560 (author)
  • Nilsson, AnnaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri(Swepub:uu)annil134 (author)
  • Vallianatou, TheodosiaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri(Swepub:uu)theva108 (author)
  • Odell, Luke R.Uppsala universitet,Preparativ läkemedelskemi(Swepub:uu)lucod220 (author)
  • Schembri, Luke SUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri(Swepub:uu)luksc280 (author)
  • Svenningsson, PerKarolinska Institutet (author)
  • Fernagut, Pierre-OlivierUniv Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France.;CNRS, Inst Malad Neurodegenerat, Bordeaux, France.;Univ Poitiers, INSERM, U0 1084, Lab Neurosci Expt & Clin, Poitiers, France. (author)
  • Crossman, Alan R.Univ Manchester, Manchester M13 9PL, Lancs, England. (author)
  • Bezard, ErwanUniv Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France.;CNRS, Inst Malad Neurodegenerat, Bordeaux, France.;Motac Neurosci, Manchester M15 6WE, Lancs, England. (author)
  • Andrén, Per E.,Professor,1957-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri(Swepub:uu)perandre (author)
  • Shariatgorji, R (author)
  • Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Related titles

  • In:Science Advances: American Association for the Advancement of Science (AAAS)7:22375-2548

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