title: From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms.
abstract: The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bilateral have not been described yet. We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats. Sequentially bilateral lesioned animals showed a bilateral increase in striatal preproenkephalin (PPE) mRNA without changes in pre-prodynorphin (PDyn) mRNA expression. The increase in dyskinesias when parkinsonism becomes bilateral was mostly due to an increase in orolingual dyskinesias associated to a increase in PDyn mRNA expression. Right lesion induces, or facilitates when first-done, a greater level of LIDs and an increase in striatal PPE and PDyn mRNAs in the second lesioned side. We describe a new striatal molecular pattern that appears when parkinsonism becomes bilateral and the relevance of the lateralization for the development of LIDs.
authors.affiliation: INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: cmarin@clinic.ub.es.
authors.forename: C
authors.initials: C
authors.lastname: Marin
authors.affiliation: INGENIO, IRCE, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bonastre
authors.affiliation: Departament de Neuroquímica i Neurofarmacologia, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: G
authors.initials: G
authors.lastname: Mengod
authors.affiliation: Departament de Neuroquímica i Neurofarmacologia, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cortés
authors.affiliation: Department of Neurology, Hospital Universitario Donostia and Neuroscience Unit, BioDonostia Research Institute, San Sebastian, Spain; Centro de Investigación en Redes sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Rodríguez-Oroz
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004399:Dynorphins / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology*; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D009043:Motor Activity / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D000978:Antiparkinson Agents; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C036448:pre-prodynorphin; D007980:Levodopa; D004399:Dynorphins; D016627:Oxidopamine; C033660:preproenkephalin
keywords: 6-Hydroxydopamine; Basal ganglia; Dyskinesia; Parkinson's disease; Preprodynorphin; Preproenkephalin