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PLoS One. 2008 Feb 13;3(2):e1589. doi: 10.1371/journal.pone.0001589.

Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.

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  • 1Department of Pharmaceutical Biosciences, Uppsala Biomedicinska Centrum (BMC), Uppsala University, Uppsala, Sweden.

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.

PMID:
18270577
PMCID:
PMC2217596
DOI:
10.1371/journal.pone.0001589
[PubMed - indexed for MEDLINE]
Free PMC Article
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