Department of Chemistry and R.N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, Kansas 66045, United States.
Department of Analytical Chemistry, UNESCO Laboratory of Environmental Electrochemistry, Charles University, Prague 2 12843, Czech Republic.
Chem Res Toxicol. 2022 Nov 21;35(11):1974-1982. doi: 10.1021/acs.chemrestox.2c00150. Epub 2022 Sep 30.
In this work, we carried out neurochemical and behavioral analysis of zebrafish () treated with rotenone, an agent used to chemically induce a syndrome resembling Parkinson's disease (PD). Dopamine release, measured with fast-scan cyclic voltammetry (FSCV) at carbon-fiber electrodes in acutely harvested whole brains, was about 30% of that found in controls. Uptake, represented by the first order rate constant () and the half-life () determined by nonlinear regression modeling of the stimulated release plots, was also diminished. Behavioral analysis revealed that rotenone treatment increased the time required for zebrafish to reach a reward within a maze by more than 50% and caused fish to select the wrong pathway, suggesting that latent learning was impaired. Additionally, zebrafish treated with rotenone suffered from diminished locomotor activity, swimming shorter distances with lower mean velocity and acceleration. Thus, the neurochemical and behavioral approaches, as applied, were able to resolve rotenone-induced differences in key parameters. This approach may be effective for screening therapies in this and other models of neurodegeneration.
在这项工作中，我们对用鱼藤酮处理的斑马鱼进行了神经化学和行为分析，鱼藤酮是一种用于化学诱导类似于帕金森病 (PD) 的综合征的试剂。在急性收获的全脑的碳纤维电极上用快速扫描循环伏安法 (FSCV) 测量的多巴胺释放量约为对照组的 30%。通过对刺激释放图谱的非线性回归建模来表示的摄取，由一阶速率常数 () 和半衰期 () 确定，也减少了。行为分析表明，鱼藤酮处理使斑马鱼在迷宫中到达奖励所需的时间增加了 50%以上，并导致鱼选择了错误的路径，表明潜在的学习受到损害。此外，用鱼藤酮处理的斑马鱼的运动活性降低，游动距离更短，平均速度和加速度更低。因此，应用的神经化学和行为方法能够解决鱼藤酮诱导的关键参数差异。这种方法可能对筛选这种和其他神经退行性模型中的治疗方法有效。
