# Comparative evaluation of MPTP and rotenone as inducing agents for Parkinson's disease in adult zebrafish: Behavioural and histopathological insights

## TL;DR

This study compares MPTP and rotenone as Parkinson's disease models in zebrafish, showing distinct behavioral and brain effects from each toxin.

## Contribution

The study provides a comparative analysis of MPTP and rotenone in zebrafish, revealing their unique neurotoxic effects and model relevance for Parkinson's research.

## Key findings

- MPTP induced anxiety-like behavior and localized brain damage, while rotenone caused locomotor deficits and widespread but milder effects.
- Both neurotoxins showed dose-dependent neurodegeneration, with maximum effects observed at highest doses between Day 14 and Day 22.
- Rotenone exposure led to more severe bradykinesia and C-bend impairments compared to MPTP in zebrafish models.

## Abstract

Parkinson's disease (PD), a prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and motor impairments. This study aimed to establish and compare PD models in adult zebrafish using two neurotoxins, MPTP and rotenone, evaluating their impact on behaviour and histopathology. Zebrafish were exposed to MPTP via intraperitoneal injection at two different doses or to rotenone in water for 21 days. Behavioural assessments, including Novel Tank Diving Test, bradykinesia, and C-bend response, revealed progressive motor and anxiety-like impairments, with rotenone exhibiting stronger locomotor effects. Histopathological analyses confirmed dose-dependent neurodegeneration in brain regions, with MPTP showing localized damage and rotenone causing widespread but milder effects. While both neurotoxins induced PD-like phenotypes, rotenone produced more pronounced locomotor deficits, whereas MPTP triggered anxiety-like symptoms. In conclusion, our study demonstrates that MPTP induces significant locomotor dysfunction along with anxiety-like symptoms, while rotenone strongly impacts locomotion with mild anxiety effects. Both neurotoxins exhibited maximum effects at their highest doses and over a similar time frame (Day 14 to Day 22). These findings highlight the distinct neurotoxic mechanisms of MPTP and rotenone and their relevance in modelling PD pathogenesis. The zebrafish model provides a robust platform for studying neurodegenerative diseases and testing therapeutic interventions. Further studies are required to explore the molecular mechanisms underlying their neurotoxic effects and to validate these models for long-term and translational research.

•Side-by-side neurobehavioral and histopathological analysis of MPTP and rotenone in zebrafish PD model.•MPTP induced anxiety-like behaviour, while rotenone caused locomotor deficits in zebrafish model.•Chronic exposure to MPTP and rotenone showed dose-dependent neurodegeneration in zebrafish brain.•Rotenone exposure produced more severe bradykinesia and C-bend impairments than MPTP.•Optimized zebrafish protocols aid neurotoxicology studies and PD model selection for Parkinson's research.

Side-by-side neurobehavioral and histopathological analysis of MPTP and rotenone in zebrafish PD model.

MPTP induced anxiety-like behaviour, while rotenone caused locomotor deficits in zebrafish model.

Chronic exposure to MPTP and rotenone showed dose-dependent neurodegeneration in zebrafish brain.

Rotenone exposure produced more severe bradykinesia and C-bend impairments than MPTP.

Optimized zebrafish protocols aid neurotoxicology studies and PD model selection for Parkinson's research.