Department of Neurology, Philipps-University Marburg, Germany.
Brain Res. 2012 Jun 29;1464:82-8. doi: 10.1016/j.brainres.2012.05.007. Epub 2012 May 15.
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.
特发性震颤传统上被认为是基底神经节疾病，但越来越多的证据表明小脑功能障碍也可能在这种疾病的发病机制中起着关键作用。我们现在证明，慢性向大鼠小脑蚓部应用红藻氨酸可导致持久和广泛的肌张力障碍运动表型，并对这种新的肌张力障碍动物模型进行了详细的特征描述。c-fos 表达作为神经元激活的标志物，不仅在小脑本身增加，而且在前腹侧丘脑增加，进一步支持了发病机制中存在紊乱的神经网络的假设。纹状体中前脑啡肽原的表达减少，但前强啡肽原的表达保持不变，这表明在我们的模型系统中，间接但不是直接的基底神经节通路发生了继发性变化。热休克蛋白 70 的表达特异性增加，出现在浦肯野细胞层和红核中。这种新的肌张力障碍大鼠模型不仅可用于进一步研究小脑在肌张力障碍发病机制中的作用，还可用于评估化合物在延长、广泛的肌张力障碍啮齿动物模型中对肌张力障碍的有益作用。
