Bashirzade Alim A O, Cheresiz Sergey V, Belova Alisa S, Drobkov Alexey V, Korotaeva Anastasiia D, Azizi-Arani Soheil, Azimirad Amirhossein, Odle Eric, Gild Emma-Yanina V, Ardashov Oleg V, Volcho Konstantin P, Bozhko Dmitrii V, Myrov Vladislav O, Kolchanova Sofia M, Polovian Aleksander I, Galumov Georgii K, Salakhutdinov Nariman F, Amstislavskaya Tamara G, Kalueff Allan V
Scientific Research Institute of Neuroscience and Medicine, 630090 Novosibirsk, Russia.
Institute of Medicine and Psychology, Novosibirsk State University, 630117 Novosibirsk, Russia.
Toxics. 2022 Feb 4;10(2):69. doi: 10.3390/toxics10020069.
The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson's disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-μg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes.
斑马鱼是生物医学研究中一种很有前景的模式生物，包括神经毒理学和神经活性药物筛选。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会引发多巴胺能神经元变性，常用于在包括斑马鱼在内的实验动物中模拟帕金森病（PD）。然而，MPTP诱发的实验性PD模型中的认知表型仍知之甚少。在此，我们确定了成年斑马鱼腹腔注射MPTP的半数致死剂量（LD，292 mg/kg），并报告了在使用200 μg该药物处理的鱼类的PD模型中，空间工作记忆受损（在Y迷宫中自发交替能力较差）。除了传统的行为分析外，我们还采用基于人工智能（AI）的方法，在Y迷宫测试期间独立且无偏差地表征MPTP对斑马鱼行为的影响。这些分析产生了一个针对200 μg MPTP（与其他组相比）组的独特聚类，表明高剂量MPTP产生了斑马鱼游泳的独特的、可通过计算检测到的模式。总的来说，这些发现支持将成年斑马鱼中的MPTP处理作为一种具有明显认知表型的晚期实验性PD模型。
