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Public Library of Science, PLoS ONE, 2(3), p. e1589, 2008

DOI: 10.1371/journal.pone.0001589

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Striatal Proteomic Analysis Suggests that First L-Dopa Dose Equates to Chronic Exposure

Journal article published in 2008 by Birger Scholz, Marcus Svensson, Henrik Alm, Karl Sköld, Maria Fälth, Kim Kultima, Céline Guigoni, Evelyne Doudnikoff ORCID, Qin Li, Alan R. Crossman, Erwan Bezard ORCID, Per E. Andrén, Svensson M Alm H Sköld K Fälth M Kultima K Guigoni C Doudnikoff E Li Q Crossman AR Bezard E Andrén Pe Scholz B.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.