Generation of Mitochondrial Toxin Rodent Models of Parkinson’s Disease Using 6-OHDA, MPTP, and Rotenone

Maegawa, Hiroharu; Niwa, Hitoshi

doi:10.1007/978-1-0716-1495-2_10

Cited by 17 publications

(10 citation statements)

References 46 publications

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“…Much evidence has shown that the antioxidant molecule glutathione (GSH) can prevent and treat DA neurodegeneration induced by various neurotoxins, such as 6-OHDA, MPTP, and rotenone [ 43 ]. Our further analysis found that the antioxidant property of NCS was also primarily achieved by raising the level of GSH in cells and nematodes.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Tsai

Liu

et al. 2022

Antioxidants

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We assessed the antioxidant potential of narcissoside from Sambucus nigra flowers (elderflowers) in Parkinson’s disease models in vitro and in vivo. The results showed that narcissoside lessened the 6-hydroxydopamine (6-OHDA)-induced increase in reactive oxygen species (ROS) and apoptosis in SH-SY5Y cells. In the 6-OHDA-exposed Caenorhabditis elegans model, narcissoside reduced degeneration of dopaminergic neurons and ROS generation, and also improved dopamine-related food-sensitive behavior and shortened lifespan. Moreover, NCS increased total glutathione (GSH) by increasing the expression of the catalytic subunit and modifier subunit of γ-glutamylcysteine ligase in cells and nematodes. Treatment with a GSH inhibitor partially abolished the anti-apoptotic ability of narcissoside. Furthermore, narcissoside diminished the 6-OHDA-induced phosphorylation of JNK and p38, while rising activities of ERK and Akt in resisting apoptosis. The antioxidant response element (ARE)-luciferase reporter activity analysis and electromobility gel shift assay showed that narcissoside promotes the transcriptional activity mediated by Nrf2. Finally, we found that narcissoside augmented the expression of miR200a, a translational inhibitor of the Nrf2 repressor protein Keap1. Downregulation of Nrf2 and miR200a by RNAi and anti-miR200a, respectively, reversed the neuroprotective ability of narcissoside. In summary, narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, alleviate 6-OHDA-induced apoptosis, and has the neuroprotective potential.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Tsai

Liu

et al. 2022

Antioxidants

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“…The injected toxins include 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, rotenone, and so on [14,15]. Rotenone and MPTP show little difference in their ability to use and inhibit the respiratory chain in animals [16]. However, only MPTP has a clear association with the onset of human PD; in other words, human exposure to MPTP results in a syndrome similar to the core neurological symptoms of PD and relatively selective dopaminergic neurodegeneration [17].…”

Section: An Appropriate Model For Pd Neuroinflammatory Studymentioning

confidence: 99%

LncZFAS1 Inhibit MPP+-Induced Neuroinflammation Through TXNIP/MIB1 E3 Ubiquitin Ligase/NLRP3 Axis

2022

Journal of Cellular Immunology

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Neuroinflammation is associated with the occurrence and progression of Parkinson's disease (PD). Nucleotide-binding domain-like receptor protein-3 (NLRP3) is closely related to pyroptosis in PD-related cells and animal models, such as microglia and SH-SY5Y cells. The novel lncRNA ZFAS1 (LncZFAS1) regulates a variety of signaling pathways and participates in the inflammatory response in various diseases. However, their role in PD remains unclear. Our research found LncZFAS1 overexpression directly interfered with mir590-3p to inhibit thioredoxin-interacting protein (TXNIP) the Mindbomb 1 (MIB1) E3 ubiquitin ligase/NLRP3 pathway, which might reveal a new research approach to the mechanism of PD.

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“…This paradigm has found use in assessing the effects of alcohol exposure, 71 selenium exposure, 72 and modulation of dopamine receptor function on latent learning ability. 73 In this work, we have dosed zebrafish with rotenone, a mitochondrial complex I inhibitor, 74 to induce a syndrome that resembles PD. We then behaviorally analyzed treated and control fish with the latent learning paradigm to assess cognitive and locomotor impairments.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In this work, we have dosed zebrafish with rotenone, a mitochondrial complex I inhibitor, to induce a syndrome that resembles PD. We then behaviorally analyzed treated and control fish with the latent learning paradigm to assess cognitive and locomotor impairments.…”

Section: Introductionmentioning

confidence: 99%

Dopamine Release Impairments Accompany Locomotor and Cognitive Deficiencies in Rotenone-Treated Parkinson’s Disease Model Zebrafish

Hettiarachchi

Niyangoda

Jarošová

et al. 2022

Chem. Res. Toxicol.

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In this work, we carried out neurochemical and behavioral analysis of zebrafish (Danio rerio) treated with rotenone, an agent used to chemically induce a syndrome resembling Parkinson's disease (PD). Dopamine release, measured with fast-scan cyclic voltammetry (FSCV) at carbon-fiber electrodes in acutely harvested whole brains, was about 30% of that found in controls. Uptake, represented by the first order rate constant (k) and the half-life (t 1/2 ) determined by nonlinear regression modeling of the stimulated release plots, was also diminished. Behavioral analysis revealed that rotenone treatment increased the time required for zebrafish to reach a reward within a maze by more than 50% and caused fish to select the wrong pathway, suggesting that latent learning was impaired. Additionally, zebrafish treated with rotenone suffered from diminished locomotor activity, swimming shorter distances with lower mean velocity and acceleration. Thus, the neurochemical and behavioral approaches, as applied, were able to resolve rotenone-induced differences in key parameters. This approach may be effective for screening therapies in this and other models of neurodegeneration.

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Generation of Mitochondrial Toxin Rodent Models of Parkinson’s Disease Using 6-OHDA, MPTP, and Rotenone

Cited by 17 publications

References 46 publications

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

LncZFAS1 Inhibit MPP+-Induced Neuroinflammation Through TXNIP/MIB1 E3 Ubiquitin Ligase/NLRP3 Axis

Dopamine Release Impairments Accompany Locomotor and Cognitive Deficiencies in Rotenone-Treated Parkinson’s Disease Model Zebrafish

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