Delis F, Mitsacos A, Giompres P
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, 26500 Rion, Greece.
Neuroscience. 2004;125(1):255-68. doi: 10.1016/j.neuroscience.2004.01.020.
The Purkinje Cell Degeneration (Nna1pcd, pcd) mutant mouse is mainly characterized by the complete, primary loss of the Purkinje cells and the secondary, partial, retrograde loss of the granule and inferior olive neurons and is considered a model of human degenerative ataxia. We determined, by in vitro quantitative autoradiography and in situ hybridization, the effects of the Purkinje cell deprivation on the dopaminergic system of the Nna1pcd mutant mouse. The dopamine transporters, as determined by [3H]WIN35428 binding, were increased compared with wild-type mice in the ventral mesencephalic dopaminergic nuclei and in the lateral striatum, motor cortex and septum. In the cerebellum of Nna1pcd mice, the dopamine transporters showed a significant increase in the deep cerebellar nuclei, but were significantly decreased in the molecular layer. The D1-like receptors, as determined by [3H]SCH23390 binding, increased significantly in the Nna1pcd substantia nigra. The D2/D3 receptors, as determined by [3H]raclopride binding, exhibited a significant decrease in lateral divisions of the striatum. Significant increases in D2-like receptors, as determined by [3H]nemonapride binding, were observed in most divisions of the striatum as well as in septum, hippocampus, and piriform cortex. This D2-like fraction most probably corresponds to the D4 receptor subtype. In the cerebellum of Nna1pcd mice, D2-like receptors were significantly decreased in the molecular layer. The results suggest an increased excitatory input on the dopaminergic mesencephalic neurons and an alteration of the dopaminergic neurotransmission in basal ganglia, cortical and limbic regions of the Nna1pcd mutant mouse. In the cerebellum, the significant downregulation of the dopamine transporters and D2-like receptors in the mutant cerebellar molecular layer is possibly due to the absence of the Purkinje cells.
浦肯野细胞变性（Nna1pcd，pcd）突变小鼠的主要特征是浦肯野细胞完全原发性丧失，以及颗粒细胞和下橄榄核神经元继发性、部分逆行性丧失，被认为是人类退行性共济失调的模型。我们通过体外定量放射自显影和原位杂交，确定了浦肯野细胞缺失对Nna1pcd突变小鼠多巴胺能系统的影响。通过[3H]WIN35428结合测定，腹侧中脑多巴胺能核、外侧纹状体、运动皮层和隔区的多巴胺转运体与野生型小鼠相比有所增加。在Nna1pcd小鼠的小脑中，多巴胺转运体在小脑深部核团显著增加，但在分子层显著减少。通过[3H]SCH23390结合测定，D1样受体在Nna1pcd黑质中显著增加。通过[3H]雷氯必利结合测定，D2/D3受体在纹状体外侧部显著减少。通过[3H]奈莫必利结合测定，在纹状体的大多数区域以及隔区、海马和梨状皮层观察到D2样受体显著增加。这个D2样部分很可能对应于D4受体亚型。在Nna1pcd小鼠的小脑中，分子层的D2样受体显著减少。结果表明，Nna1pcd突变小鼠的多巴胺能中脑神经元兴奋性输入增加，基底神经节、皮层和边缘区域的多巴胺能神经传递发生改变。在小脑中，突变小鼠小脑分子层多巴胺转运体和D2样受体的显著下调可能是由于浦肯野细胞的缺失。
