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Transcriptional alterations under continuous or pulsatile dopaminergic treatment in dyskinetic rats

Grünblatt, E. ; Schmidt, W. ; Scheller, D. ; Riederer, P. ; Gerlach, M.

In: Journal of Neural Transmission, 2011, vol. 118, no. 12, p. 1717-1725

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    Title
    • Transcriptional alterations under continuous or pulsatile dopaminergic treatment in dyskinetic rats
    Author
    • Grünblatt, E.. Neurochemistry Laboratory, Department of Psychiatry, Psychosomatics and Psychotherapy, National Parkinson Foundation Centre of Excellence Laboratories, University of Würzburg, Würzburg, Germany
    • Schmidt, W.. Department of Neuropharmacology, Zoological Institute, University of Tübingen, Tübingen, Germany
    • Scheller, D.. UCB Pharma SA, CNS research, Braine l'Alleud, Belgium
    • Riederer, P.. Neurochemistry Laboratory, Department of Psychiatry, Psychosomatics and Psychotherapy, National Parkinson Foundation Centre of Excellence Laboratories, University of Würzburg, Würzburg, Germany
    • Gerlach, M.. Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:317995
    Summary
    Continuous dopaminergic treatment is considered to prevent or delay the occurrence of dyskinesia in patients with Parkinson's disease (PD). Rotigotine is a non-ergolinic D3>D2>D1 dopamine-receptor agonist for the treatment of PD using a transdermal delivery system providing stable plasma levels. We aimed to investigate the differential influence on gene expression of pulsatile l-DOPA or rotigotine versus a continuous rotigotine treatment. The gene expression profile within the nigro-striatal system of unilateral 6-hydroxydopamine-lesioned rats was assessed in order to differentiate potential changes in gene expression following the various treatment using Affymetrix microarrays and quantitative RT-PCR. The expression of 15 genes in the substantia nigra and of 11 genes in the striatum was altered under pulsatile treatments inducing dyskinetic motor response, but was unchanged under continuous rotigotine treatment that did not cause dyskinetic motor response. The route of administration of a dopaminergic drug is important for the induction or prevention of motor abnormalities and adaptive gene expressions. The decline of neurotrophin-3 expression under pulsatile administration was considered of particular importance