Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model

Wang, Qiang; Liu, Shuai; D, Hu; Wang, Zhen; Wu, Tianfu; Wu, Zhuanbin; Mohan, Chandra; Peng, Ai

doi:10.1016/j.lfs.2016.06.009

Cited by 31 publications

(15 citation statements)

References 36 publications

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“…It is important to note that 0.04 mg/L was the observed LC50 in this study, which suggests that the observed effect may be due to lethality or malformation of the embryos and not directly caused by paraquat. Another study found that exposure to 100 mg/L at 72 hpf caused activation of oxidative stress related genes after 24 h of treatment [45]. A more recent study showed that transgenic zebrafish Tg(dat:EGFP) treated with 257 mg/L of paraquat had decreased expression of th and dat and a reduction in total DA neurons with a reduction in overall decrease of fish size [46].…”

Section: Paraquat and Rotenonementioning

confidence: 99%

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Wasel

Freeman

2020

IJMS

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The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system.

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Section: Paraquat and Rotenonementioning

confidence: 99%

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Wasel

Freeman

2020

IJMS

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“…These exhibit a normal number of dopaminergic neurons, normal behavior, and no developmental defects ( 31 ). Instead, when the LC 50 of paraquat is used, zebrafish larvae exhibit a reduction of the dopamine and serotonin levels, activation of antioxidant and oxidative stress related genes, and distinct macrophage activation and migration ( 55 , 56 ). In addition, significant increase of apoptotic cells in the head, trunk, and tail, and motor deficits are observed.…”

Section: Zebrafish As a Model Of Hypokinetic Movement Disordersmentioning

confidence: 99%

Zebrafish as an Animal Model for Drug Discovery in Parkinson’s Disease and Other Movement Disorders: A Systematic Review

2018

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Movement disorders can be primarily divided into hypokinetic and hyperkinetic. Most of the hypokinetic syndromes are associated with the neurodegenerative disorder Parkinson’s disease (PD). By contrast, hyperkinetic syndromes encompass a broader array of diseases, including dystonia, essential tremor, or Huntington’s disease. The discovery of effective therapies for these disorders has been challenging and has also involved the development and characterization of accurate animal models for the screening of new drugs. Zebrafish constitutes an alternative vertebrate model for the study of movement disorders. The neuronal circuitries involved in movement in zebrafish are well characterized, and most of the associated molecular mechanisms are highly conserved. Particularly, zebrafish models of PD have contributed to a better understanding of the role of several genes implicated in the disease. Furthermore, zebrafish is a vertebrate model particularly suited for large-scale drug screenings. The relatively small size of zebrafish, optical transparency, and lifecycle, are key characteristics that facilitate the study of multiple compounds at the same time. Several transgenic, knockdown, and mutant zebrafish lines have been generated and characterized. Therefore, it is central to critically analyze these zebrafish lines and understand their suitability as models of movement disorders. Here, we revise the pathogenic mechanisms, phenotypes, and responsiveness to pharmacotherapies of zebrafish lines of the most common movement disorders. A systematic review of the literature was conducted by including all studies reporting the characterization of zebrafish models of the movement disorders selected from five bibliographic databases. A total of 63 studies were analyzed, and the most relevant data within the scope of this review were gathered. The majority (62%) of the studies were focused in the characterization of zebrafish models of PD. Overall, the zebrafish models included display conserved biochemical and neurobehavioral features of the phenomenology in humans. Nevertheless, in light of what is known for all animal models available, the use of zebrafish as a model for drug discovery requires further optimization. Future technological developments alongside with a deeper understanding of the molecular bases of these disorders should enable the development of novel zebrafish lines that can prove useful for drug discovery for movement disorders.

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“…Most notably, inflammation – which would be present in any disease state with a requirement for drug delivery – is known to result in increased levels of the chemokines macrophage migration inhibitory factor (MIF) and/or macrophage chemotactic protein (MCP-1 or CCL2), which are strong signals for macrophage recruitment into the tissue (Lee et al, 2010; Baeck et al, 2012). Additionally, oxidative stress – which is a known complication of both chronic disease and infection (Nimse and Pal, 2015; Petersen and Smith, 2016) – have been shown to initiate macrophage migration in vivo (Wang et al, 2016). In terms of systemic migration toward chemotactic signals originating from hypoxic tissue, such as in cancer, evidence also exist to confirm the inherent capacity of macrophages to migrate toward tumors (Owen et al, 2004; Batrakova et al, 2011).…”

Section: Components Of a Cell-based Delivery Systemmentioning

confidence: 99%

“…Clearly, a model proposing quite significant paradigm shifts, such as the one we described here, requires substantial in vitro and in vivo testing and optimization by multiple laboratories. Given the requirement for in vivo tracking of cells, a zebrafish model may be the ideal choice for pilot studies, as the basic anatomy of the fish facilitates leukocyte migration tracking (Langenau et al, 2004) and this model has been employed in the context of macrophage migration (Wang et al, 2016; Barros-Becker et al, 2017). Additionally, in vivo tracking can also be achieved by permanent intracellular cell labeling and/or lasing techniques (Schubert et al, 2015) that would elucidate the exact location of carrier macrophages as well as their cargo over an extended period of time.…”

Section: Post-delivery Clearance Of the Systemmentioning

confidence: 99%

Harnessing Macrophages for Controlled-Release Drug Delivery: Lessons From Microbes

2019

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With the effectiveness of therapeutic agents ever decreasing and the increased incidence of multi-drug resistant pathogens, there is a clear need for administration of more potent, potentially more toxic, drugs. Alternatively, biopharmaceuticals may hold potential but require specialized protection from premature in vivo degradation. Thus, a paralleled need for specialized drug delivery systems has arisen. Although cell-mediated drug delivery is not a completely novel concept, the few applications described to date are not yet ready for in vivo application, for various reasons such as drug-induced carrier cell death, limited control over the site and timing of drug release and/or drug degradation by the host immune system. Here, we present our hypothesis for a new drug delivery system, which aims to negate these limitations. We propose transport of nanoparticle-encapsulated drugs inside autologous macrophages polarized to M1 phenotype for high mobility and treated to induce transient phagosome maturation arrest. In addition, we propose a significant shift of existing paradigms in the study of host-microbe interactions, in order to study microbial host immune evasion and dissemination patterns for their therapeutic utilization in the context of drug delivery. We describe a system in which microbial strategies may be adopted to facilitate absolute control over drug delivery, and without sacrificing the host carrier cells. We provide a comprehensive summary of the lessons we can learn from microbes in the context of drug delivery and discuss their feasibility for in vivo therapeutic application. We then describe our proposed “synthetic microbe drug delivery system” in detail. In our opinion, this multidisciplinary approach may hold the solution to effective, controlled drug delivery.

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Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model

Cited by 31 publications

References 36 publications

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Zebrafish as an Animal Model for Drug Discovery in Parkinson’s Disease and Other Movement Disorders: A Systematic Review

Harnessing Macrophages for Controlled-Release Drug Delivery: Lessons From Microbes

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