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在 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的斑马鱼模型中神经行为模式的特征:96 小时行为研究。

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study.

机构信息

Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.

Department of Biotechnology, Kulliyyah of Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.

出版信息

PLoS One. 2022 Oct 3;17(10):e0274844. doi: 10.1371/journal.pone.0274844. eCollection 2022.

Abstract

Parkinson's disease (PD) is the most common brain motor disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Motor impairments, such as dyskinesia, bradykinesia, and resting tremors, are the hallmarks of PD. Despite ongoing research, the exact PD pathogenesis remains elusive due to the disease intricacy and difficulty in conducting human studies. Zebrafish (Danio rerio) has emerged as an ideal model for researching PD pathophysiology. Even though 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used to induce PD in zebrafish, behavioural findings are frequently limited to a single time point (24 hours post-injection). In this sense, we aim to demonstrate the effects of MPTP on zebrafish swimming behaviour at multiple time points. We administered a single dosage of MPTP (200μg/g bw) via intraperitoneal injection (i/p) and assessed the locomotor activity and swimming pattern at 0h, 24h, and 96h post-injection through an open field test. Analysis of the behaviour revealed significant reductions in swimming velocity (cm/s) and distance travelled (cm), concurrent with an increase in freezing maintenance (duration and bouts) in zebrafish injected with MPTP. In addition, the MPTP-injected zebrafish exhibited complex swimming patterns, as measured by the turn angle, meander, and angular velocity, and showed abnormal swimming phenotypes, including freezing, looping, and erratic movement. To conclude, MPTP administration into adult zebrafish induced hypolocomotion and elicited motor incoordination. Plus, the effects of MPTP were observable 24 hours after the injection and still detectable 96 hours later. These findings contribute to the understanding of MPTP effects on adult zebrafish, particularly in terms of swimming behaviours, and may pave the way for a better understanding of the establishment of PD animal models in the future.

摘要

帕金森病(PD)是最常见的大脑运动障碍,其特征是黑质致密部(SNpc)中多巴胺能神经元大量丧失。运动障碍,如运动徐缓、运动不能和静止性震颤,是 PD 的标志。尽管正在进行研究,但由于疾病的复杂性和进行人体研究的难度,确切的 PD 发病机制仍难以捉摸。斑马鱼(Danio rerio)已成为研究 PD 病理生理学的理想模型。尽管 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)已被用于诱导斑马鱼 PD,但行为发现通常仅限于单一时间点(注射后 24 小时)。在这种意义上,我们旨在展示 MPTP 对斑马鱼游泳行为的影响在多个时间点。我们通过腹腔内注射(i/p)给予单次剂量的 MPTP(200μg/g bw),并通过旷场测试在注射后 0h、24h 和 96h 评估运动活性和游泳模式。行为分析表明,注射 MPTP 的斑马鱼的游泳速度(cm/s)和行进距离(cm)显著降低,同时冻结维持时间(持续时间和发作)增加。此外,MPTP 注射的斑马鱼表现出复杂的游泳模式,如转弯角度、曲折和角速度,并表现出异常的游泳表型,包括冻结、循环和不稳定运动。总之,MPTP 给药至成年斑马鱼可引起运动减少和运动协调障碍。此外,MPTP 的作用在注射后 24 小时即可观察到,96 小时后仍可检测到。这些发现有助于理解 MPTP 对成年斑马鱼的影响,特别是在游泳行为方面,并且可能为未来更好地理解 PD 动物模型的建立铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/354b/9529090/57e47a71ed3d/pone.0274844.g001.jpg

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