title: Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats.
abstract: Multiple genetic deficits have linked impaired ubiquitin-conjugation pathways to various forms of familiar Parkinson's disease. We therefore examined the possible role of 6-hydroxydopamine, a dopaminergic neurotoxin used in Parkinson's disease experimental models, in causing protein degradation and its association with the ubiquitin proteasome system. Using unilaterally 6-hydroxydopamine-denervated rats and mass spectrometry profiling directly on brain tissue sections, we here report for the first time an increased level of unconjugated ubiquitin specifically in the dorsal striatum of the dopamine depleted hemisphere. No similar changes were found in the intact hemisphere or in the ventral striatum of the dopamine depleted hemisphere. The lesioning of the dopamine innervation to the striatum was confirmed by a strongly reduced dopamine transporter binding in the striatum, indicating an abundant loss of dopamine neurons. These results suggest that denervation of dopamine neurons per se is implicated in the regulation of ubiquitin pathways, at least in a classical animal model of Parkinson's disease. This study adds additional information regarding the involvement of the ubiquitin-proteasome system in Parkinson's disease.
authors.affiliation: Laboratory for Biological and Medical Mass Spectrometry, Uppsala University, Box 583 Biomedical Centre, SE-75123 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Pierson
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.forename: Per E
authors.initials: PE
authors.lastname: Andren
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D016627:Oxidopamine