Transient MPTP exposure at a sensitive developmental window altered gut microbiome and led to male-biased motor and social behavioral deficits in adult zebrafish

Dong, Haojia; Wu, Hongmiao; Bai, Chenglian; Ye, Kaiwei; Mao, Luying; Lei, Yuhang; Liu, Yi; Xu, Hui; Lin, Jian; Zhu, Jian-Hong; Dong, Qian

doi:10.1016/j.neuro.2022.06.008

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…This indicates that, on the 96 th hour, instead of alternating between swimming and freezing, the MPTP-injected zebrafish were predominantly immobile during the whole duration of the behavior test. Our finding is in line with those of previous studies, which documented hypolocomotion in neurotoxin-induced animal models [ 25 , 28 – 30 ]. Anichtchik et al [ 25 ] found a substantial decrease in locomotor activity and an increase in turn angle in MPTP-injected zebrafish on the 1 st , 3 rd , 6 th , and 9 th days following injection.…”

Section: Discussionsupporting

confidence: 93%

“…In terms of locomotion, zebrafish exhibit sophisticated behaviours reflective of PD. A number of studies have reported the effects of MPTP on zebrafish locomotion [ 18 , 19 , 21 , 25 , 30 ], but only a few have performed prolonged observation [ 21 , 25 ]. Assessing the behavioural changes at several time points is critical as it provides stronger evidence for the establishment of MPTP-induced zebrafish model of PD.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…To investigate early in-live roles of Panx1 when mitochondrial function and metabolism are disrupted, we treated six-day-old Tubingen Longfin (TL) larvae with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) to induce rapid neurotoxicity 43 . We leveraged multiple advantages of zebrafish models as a translational model for fundamental process discovery.…”

Section: Introductionmentioning

confidence: 99%

“…A Power spectral density (PSD) estimation was performed by the Welch's method for baseline and MPTP recordings. A moving window for fast Fourier transform (FFT) computation was used and all windows were averaged.The frequency bands theta (3.5-7.5 Hz), beta (12-30 Hz) and gamma(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) were extracted for analysis using NeuroExplorer Version 4 (Nex Technologies, Colorado Springs, CO, 80906, USA). Changes in PSD between baseline and treatment were analyzed for significance using a Welch's t-test.…”

mentioning

confidence: 99%

Panx1 deletion promotes synaptic reconfiguration and recruitment of cell death pathways in the Zebrafish MPTP model

Zoidl,

Safarian,

Zoidl

et al. 2024

Preprint

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Pannexin-1 (Panx1) channels have garnered attention for their implications in neurodegeneration, potentially with a role in mediating the delicate balance between cell death and survival. However, a comprehensive understanding of the underlying molecular and cellular mechanisms remains elusive, and whether Panx1 exhibits dual protective and toxic roles throughout the lifespan remains to be determined. To address these gaps, we focused on early-life changes in zebrafish larvae with impaired Panx1a function subjected to acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. We demonstrate that a single four-hour exposure to MPTP induces substantial alterations in locomotor behavior, the transcriptome, and local field potentials within the ascending visual pathway. KEGG pathway analysis underscored MPTP's regulatory influence on neurodegeneration; here the differential expression of biomarkers for Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease, suggested a protective role of Panx1a ablation. However, the potential beneficial impact of targeting Panx1a is superseded by the deregulation of oxidative phosphorylation, glycolysis, ROS, hypoxia, unfolded protein response pathways, and reduced extracellular ATP. Notably, these changes correlate with a loss of synaptic neurotransmitter receptor and ion channel/transaporter expression and the differential expression of mTORC1, autophagy, and apoptosis signaling pathways. The resultant cell death was demonstrated by acridine orange dye uptake and in-vivo imaging, with a pronounced loss of cells observed in the pallium and tectum regions. Dual recordings of local field potentials across the optic tectum and pallium demonstrate Panx1a's involvement in modulating local neuronal networks. Collectively, our results shed light on the impacts of acute MPTP treatment on locomotor behavior, transcriptomic shifts, metabolic disturbances, and the pivotal role of Panx1a in neurodegeneration and cell death. These insights enhance our comprehension of the intricate molecular and cellular mechanisms underpinning neurodegeneration, with implications for potential therapeutic strategies targeting Panx1 channels in the context of neuroinflammatory pathologies.

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Utility of zebrafish-based models in understanding molecular mechanisms of neurotoxicity mediated by the gut–brain axis

Adedara,

Mohammed,

Canzian

et al. 2024

Advances in Neurotoxicology

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Transient MPTP exposure at a sensitive developmental window altered gut microbiome and led to male-biased motor and social behavioral deficits in adult zebrafish

Cited by 6 publications

References 33 publications

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

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

Panx1 deletion promotes synaptic reconfiguration and recruitment of cell death pathways in the Zebrafish MPTP model

Utility of zebrafish-based models in understanding molecular mechanisms of neurotoxicity mediated by the gut–brain axis

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