Kozina E A, Khaindrava V G, Kudrin V S, Kucherianu V G, Klodt P D, Bocharov E V, Raevskiĭ K S, Kryzhanovskiĭ G N, Ugriumov M V
Ross Fiziol Zh Im I M Sechenova. 2010 Mar;96(3):270-82.
The dopaminergic nigrostriatal system is a key component of regulation of the motor behaviour. Cell bodies of dopaminergic DA-ergic neurons are located in the compact zone of the substantia nigra, and their axons are projected along the nigrostriatal tract to the striatum. This study was aimed to develop an experimental model of the functional insufficiency of the DA-ergic neurons of the nigrostriatal system without any manifestation of movement disorders, i.e., a model of presymptomatic stage of parkinsonism. This model has been developed with a single subcutaneous injection of a low dose of MPTP (12 mg/kg) which is converted in the brain into the MPP+, a neurotoxin of DA-ergic neurons. It has been shown that the MPTP injection on the 14th day is followed by: (a) absence of any sign of movement disorders; (b) no change in the DA content and the number of DA-ergic neurons in the substantia nigra; (c) substantial loss of DA in the striatum as a result of the degeneration of about 50% of DA-ergic axons. The absence of movement disorders under the substantial DA depletion and degradation of DA-ergic axons in the striatum is supposed to be a consequence of the turning on of the compensatory processes in the brain. Thus, we have developed the experimental model of presymptomatic stage of parkinsonism which is characterized by the degeneration of DA-ergic axons in the striatum without degradation of the neuron cell bodes in the substantia nigra.
多巴胺能黑质纹状体系统是运动行为调节的关键组成部分。多巴胺能（DA能）神经元的细胞体位于黑质致密部，其轴突沿黑质纹状体束投射至纹状体。本研究旨在建立一种黑质纹状体系统DA能神经元功能不全但无任何运动障碍表现的实验模型，即帕金森病症状前期模型。该模型通过单次皮下注射低剂量MPTP（12mg/kg）建立，MPTP在脑内转化为DA能神经元的神经毒素MPP+。结果显示，在第14天注射MPTP后：（a）无任何运动障碍迹象；（b）黑质中DA含量及DA能神经元数量无变化；（c）由于约50%的DA能轴突变性，纹状体中DA大量丢失。纹状体中DA大量耗竭及DA能轴突退化但无运动障碍，推测是脑内代偿过程启动的结果。因此，我们建立了帕金森病症状前期实验模型，其特征为纹状体中DA能轴突变性而黑质中神经元细胞体未退化。
