title: Prolonged generalized dystonia after chronic cerebellar application of kainic acid.
abstract: Dystonia has traditionally been considered as a basal ganglia disorder, but there is growing evidence that impaired function of the cerebellum may also play a crucial part in the pathogenesis of this disorder. We now demonstrate that chronic application of kainic acid into the cerebellar vermis of rats results in a prolonged and generalized dystonic motor phenotype and provide detailed characterization of this new animal model for dystonia. c-fos expression, as a marker of neuronal activation, was increased not only in the cerebellum itself, but also in the ventro-anterior thalamus, further supporting the assumption of a disturbed neuronal network underlying the pathogenesis of this disorder. Preproenkephalin expression in the striatum was reduced, but prodynorphin expression remained unaltered, suggesting secondary changes in the indirect, but not in the direct basal ganglia pathway in our model system. Hsp70 expression was specifically increased in the Purkinje cell layer and the red nucleus. This new rat model of dystonia may be useful not only for further studies investigating the role of the cerebellum in the pathogenesis of dystonia, but also to assess compounds for their beneficial effect on dystonia in a rodent model of prolonged, generalized dystonia.
authors.affiliation: Department of Neurology, Philipps-University Marburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez-Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Grundmann
authors.forename: Lixia
authors.initials: L
authors.lastname: Lu
authors.forename: Birgit
authors.initials: B
authors.lastname: Samans
authors.forename: Brita
authors.initials: B
authors.lastname: Fritsch
authors.forename: J Carsten
authors.initials: JC
authors.lastname: Möller
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schaefer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Oliver
authors.initials: O
authors.lastname: Bandmann
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004421:Dystonia / Q000139:chemically induced* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats
chemical_list: D004745:Enkephalins; D050884:HSP72 Heat-Shock Proteins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C033660:preproenkephalin; D007608:Kainic Acid