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Updated: Jul 21, 2025
Locomotor Assessment of 6-Hydroxydopamine-induced Adult Zebrafish-based Parkinson's Disease Model
Published on: December 28, 2021
Mitophagy: A Bridge Linking HMGB1 and Parkinson's Disease Using Adult Zebrafish as a Model Organism
Khairiah Razali1, Mohd Hamzah Mohd Nasir2, Jaya Kumar3
1Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM), Kuantan 25200, Pahang, Malaysia.
Abstract:
High-mobility group box 1 (HMGB1) has been implicated as a key player in two critical factors of Parkinson's disease (PD): mitochondrial dysfunction and neuroinflammation. However, the specific role of HMGB1 in PD remains elusive. We investigated the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration on mitochondrial dysfunction and HMGB1-associated inflammatory genes as well as locomotor activity in zebrafish, aiming to elucidate the role of HMGB1 in PD. Adult zebrafish received MPTP injections, and locomotor activity was measured at 24- and 48-h post-administration. Gene expression levels related to mitophagy (fis1, pink1, and park2) and HMGB1-mediated inflammation (hmgb1, tlr4, and nfkb) were quantified through RT-qPCR analysis. Following MPTP injection, the significant increase in transcript levels of fis1, pink1, and park2 indicated notable changes in PINK1/Parkin mitophagy, while the upregulation of hmgb1, tlr4, and nfkb genes pointed to the activation of the HMGB1/TLR4/NFκB inflammatory pathway. Furthermore, MPTP-injected zebrafish exhibited decreased locomotor activity, evident through reduced distance travelled, mean speed, and increased freezing durations. HMGB1 plays a major role in cellular processes as it is involved in both the mitophagy process and functions as a pro-inflammatory protein. MPTP administration in adult zebrafish activated mitophagy and inflammatory signaling, highlighting the significant role of HMGB1 as a mediator in both processes and further emphasizing its significant contribution to PD pathogenesis.
Insights
High-mobility group box 1 (HMGB1) is crucial in Parkinson's disease (PD) pathogenesis, mediating both mitophagy and neuroinflammation. MPTP administration in zebrafish activated these pathways, confirming HMGB1's significant role in PD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- High-mobility group box 1 (HMGB1) is linked to Parkinson's disease (PD) pathology, specifically mitochondrial dysfunction and neuroinflammation.
- The precise function of HMGB1 in PD pathogenesis remains unclear.
- Investigating HMGB1's role in PD requires a suitable model system to study its effects on cellular processes and behavior.
Purpose of the Study:
- To elucidate the role of High-mobility group box 1 (HMGB1) in Parkinson's disease (PD) pathogenesis.
- To investigate the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial dysfunction and HMGB1-associated inflammatory genes in zebrafish.
- To assess the effect of MPTP on locomotor activity in a zebrafish model of PD.
Main Methods:
- Adult zebrafish were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
- Locomotor activity was measured at 24 and 48 hours post-MPTP administration.
- Gene expression analysis using RT-qPCR quantified mitophagy-related genes (fis1, pink1, park2) and inflammatory genes (hmgb1, tlr4, nfkb).
Main Results:
- MPTP injection significantly increased transcript levels of mitophagy genes (fis1, pink1, park2), indicating PINK1/Parkin pathway activation.
- Upregulation of hmgb1, tlr4, and nfkb genes confirmed the activation of the HMGB1/TLR4/NFκB inflammatory pathway.
- MPTP-treated zebrafish showed reduced locomotor activity, including decreased distance traveled, lower mean speed, and increased freezing duration.
Conclusions:
- High-mobility group box 1 (HMGB1) is a key mediator in both mitophagy and inflammation, processes critical to Parkinson's disease (PD) pathogenesis.
- MPTP administration in zebrafish successfully activated mitophagy and inflammatory signaling pathways involving HMGB1.
- These findings highlight HMGB1's significant contribution to PD development and progression, underscoring its potential as a therapeutic target.
