TY - JOUR
T1 - Prolonged generalized dystonia after chronic cerebellar application of kainic acid
AU - Alvarez-Fischer, Daniel
AU - Grundmann, Michael
AU - Lu, Lixia
AU - Samans, Birgit
AU - Fritsch, Brita
AU - Möller, J. Carsten
AU - Schaefer, Martin K.H.
AU - Hartmann, Andreas
AU - Oertel, Wolfgang H.
AU - Bandmann, Oliver
PY - 2012/6/29
Y1 - 2012/6/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862003964&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2012.05.007
DO - 10.1016/j.brainres.2012.05.007
M3 - Journal articles
C2 - 22595488
AN - SCOPUS:84862003964
SN - 0006-8993
VL - 1464
SP - 82
EP - 88
JO - Brain Research
JF - Brain Research
ER -