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

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.

Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model

“…Following intraperitoneal administration of a single dose of MPTP (100 μg/g bw per fish), fish exhibited impairments in motor function as demonstrated by significant reductions in mean speed and total distance traveled. Similarly, previous studies using intraperitoneal injections of 200 μg/g bw, and intracranial injection of 25 mM MPTP in adult zebrafish also demonstrated reduced locomotor activity ( Kalyn and Ekker, 2021 ; Razali et al, 2022 ).…”

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio)

“…At the end of the study, OT-treated fish showed a decreased level of meandering, which suggests that hormone exposure had no a negative impact. A larger meander is linked with erratic movements, according to several studies where a neurotoxic impact was seen in zebrafish swimming patterns [ 72 , 73 ]. In humans, improvements in social and repetitive behaviors were observed after the administration of 24 IU OT once a day for four days and twice a day for six weeks [ 74 , 75 ].…”

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Treated Adult Zebrafish as a Model for Parkinson’s Disease

“…Instead of producing α-synuclein, zebrafish produce homologues that behave differently, namely β-synuclein (SNCB) and gamma b synuclein (SNCG1). Β-synuclein is believed to have a protective role against α-synuclein aggregation in humans 41 while gamma b synuclein has been suggested to behave similarly to human α-synuclein 42 . Both related genes were statistically downregulated in our study, which has been linked to decreased motor activity and neural DA levels in other zebrafish studies 43,44 .…”