Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, Russia.
Int J Mol Sci. 2023 Feb 3;24(3):3027. doi: 10.3390/ijms24033027.
Given the limited access to clinical material for studying the pathogenesis of Parkinson's disease (PD), these studies should be carried out on experimental models. We have recently developed a subchronic model of the progressive development of PD with a gradual transition from the preclinical (asymptomatic) stage to the clinical (symptomatic) one. The aim of this study was to evaluate changes in the expression of a wide range of genes in the substantia nigra (SN), the central link in the regulation of motor function, in mice in our subchronic model of PD. We have found changes in the expression of a number of genes encoding enzymes involved in the synthesis and degradation of dopamine as well as proteins involved in the vesicular cycle, axonal transport, protein degradation in the proteasome system, neuroinflammation, and cell death in the SN of our mouse model of the clinical stage of PD. Similar changes in gene expression were previously demonstrated in patients (postmortem), indicating good reproducibility of PD in our model. Further analysis of the gene expression in the SN of mice has shown that the expression of some genes also changes in the model of the preclinical stage, when dopaminergic neurons have not yet died. Thus, this study opens up broad prospects for further evaluation of the molecular mechanisms of PD pathogenesis and the development of a test system for drug screening.
鉴于研究帕金森病（PD）发病机制时临床材料有限，这些研究应在实验模型上进行。我们最近开发了一种具有逐渐从临床前（无症状）阶段过渡到临床（有症状）阶段的 PD 亚慢性进展模型。本研究旨在评估我们的 PD 亚慢性模型中小鼠黑质（SN）中广泛基因表达的变化，SN 是调节运动功能的中枢环节。我们发现参与多巴胺合成和降解的酶以及参与囊泡循环、轴突运输、蛋白酶体系统中蛋白质降解、神经炎症和细胞死亡的蛋白的一些基因的表达发生了变化在我们的 PD 临床阶段小鼠模型的 SN 中。先前在患者（死后）中证明了这些基因表达的类似变化，表明我们的模型中 PD 具有良好的重现性。对 SN 中基因表达的进一步分析表明，一些基因的表达在多巴胺能神经元尚未死亡的临床前阶段模型中也发生了变化。因此，这项研究为进一步评估 PD 发病机制的分子机制和药物筛选测试系统的开发开辟了广阔的前景。
