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Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2008 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 2, e1589- p.Article in journal (Refereed) Published
Abstract [en]

L-3,4-dihydroxypheylalanine (L-dopa)-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD) that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE) and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i) to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii), possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it.

Place, publisher, year, edition, pages
2008. Vol. 3, no 2, e1589- p.
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Pharmaceutical Sciences Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104848DOI: 10.1371/journal.pone.0001589ISI: 000260535900023PubMedID: 18270577OAI: oai:DiVA.org:uu-104848DiVA: diva2:220184
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2010-12-18Bibliographically approved

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