Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.
PLoS ONE. 2008-02-13; 3(2): e1589
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1. 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
Scholz B(1), Svensson M, Alm H, Sköld K, Fälth M, Kultima K, Guigoni C,
Doudnikoff E, Li Q, Crossman AR, Bezard E, Andrén PE.
(1)Department of Pharmaceutical Biosciences, Uppsala Biomedicinska Centrum (BMC),
Uppsala University, Uppsala, Sweden.
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 [Indexed for MEDLINE]