Published in
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
,
Marcus Svensson,
Henrik Alm,
Karl Sköld,
Maria Fälth,
Kim Kultima,
Céline Guigoni,
Evelyne Doudnikoff ,
Qin Li,
Alan R. Crossman,
Erwan Bezard ,
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.
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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.