Giompres Panagiotis, Delis Foteini
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Rion, Greece.
Cerebellum. 2005;4(2):105-11. doi: 10.1080/14734220510007851.
In the central nervous system, dopamine is known to play a critical role in motor and cognitive functions. Although the cerebellum plays a role in the control of movement and posture and in cognitive functions, it has not been considered to be a dopaminergic region and the dopamine present was thought to represent a precursor of noradrenaline. However, recent evidence suggests that in the cerebellum there is a small dopaminergic element, whose properties are similar to the well characterized system of striatum. In order to better understand the functional role of this system and to delineate its specific interactions within the cerebellum, the distribution and properties of dopamine transporter (DAT) in the cerebellum of reeler and Purkinje cell degeneration (Nna1pcd) mutant mice, which are characterized by severe loss of different cell populations and abnormalities in synapse formation, have been studied. Kinetic studies revealed that [3H]dopamine is transported into cerebellar synaptosomes prepared from normal mice with affinities similar to that into striatal synaptosomes but with much lower maximal velocities. In reeler cerebellar synaptosomes the number of transport sites is significantly reduced. In Nna1pcd cerebellar synaptosomes the kinetic properties of transport of [3H]dopamine are similar to the normal. However, in vitro quantitative DAT autoradiography revealed a significantly increased binding in cerebellar nuclei, a decreased binding in molecular layer and an unaltered binding in the granule cell layer. These observations confirm a dopaminergic innervation of the cerebellum and contribute to our understanding of the intracerebellar distribution of the dopaminergic system.
在中枢神经系统中，多巴胺在运动和认知功能中起着关键作用。虽然小脑在运动和姿势控制以及认知功能中发挥作用，但它一直未被视为多巴胺能区域，且其中存在的多巴胺被认为是去甲肾上腺素的前体。然而，最近的证据表明，小脑中存在一个小的多巴胺能成分，其特性与纹状体中特征明确的系统相似。为了更好地理解该系统的功能作用并描绘其在小脑中的特定相互作用，研究了reeler和浦肯野细胞变性（Nna1pcd）突变小鼠小脑中多巴胺转运体（DAT）的分布和特性，这两种小鼠的特征是不同细胞群严重缺失以及突触形成异常。动力学研究表明，[3H]多巴胺被转运到从正常小鼠制备的小脑突触体中，其亲和力与转运到纹状体突触体中的相似，但最大速度要低得多。在reeler小脑突触体中，转运位点的数量显著减少。在Nna1pcd小脑突触体中，[3H]多巴胺的转运动力学特性与正常情况相似。然而，体外定量DAT放射自显影显示，小脑核中的结合显著增加，分子层中的结合减少，颗粒细胞层中的结合未改变。这些观察结果证实了小脑的多巴胺能神经支配，并有助于我们了解多巴胺能系统在小脑中的分布情况。
