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 striat...

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Veröffentlicht in:	PloS one Jg. 3; H. 2; S. e1589
Hauptverfasser:	Scholz, Birger, Svensson, Marcus, Alm, Henrik, Sköld, Karl, Fälth, Maria, Kultima, Kim, Guigoni, Céline, Doudnikoff, Evelyne, Li, Qin, Crossman, Alan R., Bezard, Erwan, Andrén, Per E.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 13.02.2008 Public Library of Science (PLoS)
Schlagworte:	Analysis Animals Bayesian analysis Bioinformatics Chromatography Chronic exposure Corpus Striatum - chemistry Dihydroxyphenylalanine Disease Models, Animal Dopa Dopamine Dyskinesia Dyskinesia, Drug-Induced - metabolism Electrophoresis, Gel, Two-Dimensional Experiments Exposure FARMACI Fourier transforms Gel electrophoresis Gene expression Immunoglobulins L-dopa Levodopa Levodopa - administration & dosage Levodopa - adverse effects Macaca Mass Spectrometry Mass spectroscopy Movement disorders MPTP NATURAL SCIENCES NATURVETENSKAP Neostriatum Neurodegenerative diseases Neuroscience/Neurobiology of Disease and Regeneration Neurosciences Parkinson Disease - complications Parkinson Disease - drug therapy Parkinson's disease Parkinsons disease Peptides Pharmaceuticals PHARMACY Phenols (Class of compounds) Post-translation Post-translational modifications Priming Protein Processing, Post-Translational Proteins Proteomics - methods Rats Resveratrol Rodents Scientific imaging Time series
ISSN:	1932-6203, 1932-6203
Online-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: BS KK EB MS HA KS MF PA CG ED QL AC. Performed the experiments: BS KK EB MS HA KS MF CG ED QL AC. Analyzed the data: BS KK EB MS HA KS MF PA CG AC. Contributed reagents/materials/analysis tools: EB MF QL AC. Wrote the paper: BS KK EB MS HA KS PA CG ED QL AC.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0001589