title: Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.
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.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala Biomedicinska Centrum (BMC), Uppsala University, Uppsala, Sweden.
authors.forename: Birger
authors.initials: B
authors.lastname: Scholz
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson
authors.forename: Henrik
authors.initials: H
authors.lastname: Alm
authors.forename: Karl
authors.initials: K
authors.lastname: Sköld
authors.forename: Maria
authors.initials: M
authors.lastname: Fälth
authors.forename: Kim
authors.initials: K
authors.lastname: Kultima
authors.forename: Céline
authors.initials: C
authors.lastname: Guigoni
authors.forename: Evelyne
authors.initials: E
authors.lastname: Doudnikoff
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Alan R
authors.initials: AR
authors.lastname: Crossman
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Per E
authors.initials: PE
authors.lastname: Andrén
mesh_terms: 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
chemical_list: D007980:Levodopa