Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure
2008 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 2, e1589- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 3, no 2, e1589- p.
Pharmaceutical Sciences Natural Sciences
IdentifiersURN: urn:nbn:se:uu:diva-104848DOI: 10.1371/journal.pone.0001589ISI: 000260535900023PubMedID: 18270577OAI: oai:DiVA.org:uu-104848DiVA: diva2:220184