Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.
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.
Scholz
Birger
B
Department of Pharmaceutical Biosciences, Uppsala Biomedicinska Centrum (BMC), Uppsala University, Uppsala, Sweden.
Svensson
Marcus
M
Alm
Henrik
H
Sköld
Karl
K
Fälth
Maria
M
Kultima
Kim
K
Guigoni
Céline
C
Doudnikoff
Evelyne
E
Li
Qin
Q
Crossman
Alan R
AR
Bezard
Erwan
E
Andrén
Per E
PE
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D008251:Macaca; D013058:Mass Spectrometry; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D051381:Rats
D007980:Levodopa