A novel model of demyelination and remyelination in a GFP-transgenic zebrafish

Fang, Yinshan; Lei, Xudan; Li, Xiang; Chen, Yanan; Xu, Fei; Feng, Xizeng; Wei, Shimin; Li, Yuhao

doi:10.1242/bio.201410736

Cited by 24 publications

(33 citation statements)

References 34 publications

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“…The angular velocity represents the amount of turning per unit time. 17 The total movement distance, velocity, and angular velocity decreased significantly in the exposed larvae in a dose-dependent manner ( Figure 6C-E). Combined with the digital tracks and heat maps ( Figure 6A and B), these results showed that larvae from the two exposed groups were less active compared with larvae from the unexposed group.…”

mentioning

confidence: 88%

“…Whole-mount in situ hybridization was performed using a standard protocol. 17,18 A ceruloplasmin (cp, GenBank NM_131802) probe was used to label the hepatocytes. The cDNA encoding cp was linearized with SacI, and a riboprobe was synthesized with T7 polymerase.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…The system noise was filtered out at a minimum movement distance of 0.2 mm. 17 Six parameters, including total movement distance, velocity, angular velocity, fast movement time, medium movement time, and slow movement time, were analyzed. The behavioral test described earlier was repeated three times.…”

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confidence: 99%

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Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Zhang¹,

He²,

Wang³

et al. 2016

IJN

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Copper oxide nanoparticles (CuO NPs) are used for a variety of purposes in a wide range of commercially available products. Some CuO NPs probably end up in the aquatic systems, thus raising concerns about aqueous exposure toxicity, and the impact of CuO NPs on liver development and neuronal differentiation remains unclear. In this study, particles were characterized using Fourier transform infrared spectra, scanning electron microscopy, and transmission electron microscopy. Zebrafish embryos were continuously exposed to CuO NPs from 4 hours postfertilization at concentrations of 50, 25, 12.5, 6.25, or 1 mg/L. The expression of gstp1 and cyp1a was examined by quantitative reverse transcription polymerase chain reaction. The expression of tumor necrosis factor alpha and superoxide dismutase 1 was examined by quantitative reverse transcription polymerase chain reaction and Western blotting. Liver development and retinal neurodifferentiation were analyzed by whole-mount in situ hybridization, hematoxylin–eosin staining, and immunohistochemistry, and a behavioral test was performed to track the movement of larvae. We show that exposure of CuO NPs at low doses has little effect on embryonic development. However, exposure to CuO NPs at concentrations of 12.5 mg/L or higher leads to abnormal phenotypes and induces an inflammatory response in a dose-dependent pattern. Moreover, exposure to CuO NPs at high doses results in an underdeveloped liver and a delay in retinal neurodifferentiation accompanied by reduced locomotor ability. Our data demonstrate that short-term exposure to CuO NPs at high doses shows hepatotoxicity and neurotoxicity in zebrafish embryos and larvae.

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confidence: 88%

Section: In Situ Hybridizationmentioning

confidence: 99%

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Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Zhang¹,

He²,

Wang³

et al. 2016

IJN

Self Cite

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“…To test the regenerative potential of OLs and track remyelination in vivo, OLs can be genetically ablated using the nitroreductase (NTR)-mediated cell ablation techniques (Chung et al, 2013; Fang et al, 2014; Kim et al, 2015). Briefly, transgenic fish express NTR, a bacterial enzyme, in myelinating glia.…”

Section: Plasticity Maintenance and Regeneration Of Myelinated Amentioning

confidence: 99%

Analysis of myelinated axon formation in zebrafish

D’Rozario

Monk

Petersen

2017

The Zebrafish - Disease Models and Chemical Screens

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Myelin is a lipid-rich sheath formed by the spiral wrapping of specialized glial cells around axon segments. Myelinating glia allow for rapid transmission of nerve impulses and metabolic support of axons, and the absence of or disruption to myelin results in debilitating motor, cognitive, and emotional deficits in humans. Because myelin is a jawed vertebrate innovation, zebrafish are one of the simplest vertebrate model systems to study the genetics and development of myelinating glia. The morphogenetic cellular movements and genetic program that drive myelination are conserved between zebrafish and mammals, and myelin develops rapidly in zebrafish larvae, within 3–5 days post-fertilization. Myelin ultrastructure can be visualized in the zebrafish from larval to adult stages via transmission electron microscopy, and the dynamic development of myelinating glial cells may be observed in vivo via transgenic reporter lines in zebrafish larvae. Zebrafish are amenable to genetic and pharmacological screens, and screens for myelinating glial phenotypes have revealed both genes and drugs that promote myelin development, many of which are conserved in mammalian glia. Recently, zebrafish have been employed as a model to understand the complex dynamics of myelinating glia during development and regeneration. In this chapter, we describe these key methodologies and recent insights into mechanisms that regulate myelination using the zebrafish model.

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“…We chose to study the response to demyelination of reticulospinal axons in the zebrafish CNS, as reticulospinal axons represent a discrete, well-defined identifiable population that are robustly myelinated along their length by just 5 days post-fertilisation (dpf) [56]. Using the nitroreductase-metronidaxole system [57], similar to approaches recently described in both zebrafish and Xenopus laevis [58–61], we were able to ablate 2/3rds of myelinating oligodendrocytes in the larval zebrafish spinal cord at early larval stages. This ablation of oligodendrocytes was characterised over the subsequent week by widespread myelin vacuolation, axonal demyelination, and a macrophage-microglial inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber

et al. 2017

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Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons. Here we describe a larval zebrafish model of demyelination and remyelination. We employ a drug-inducible cell ablation system with which we can consistently ablate 2/3rds of oligodendrocytes in the larval zebrafish spinal cord. This leads to a concomitant demyelination of 2/3rds of axons in the spinal cord, and an innate immune response over the same time period. We find restoration of the normal number of oligodendrocytes and robust remyelination approximately two weeks after induction of cell ablation, whereby myelinated axon number is restored to control levels. Remarkably, we find that myelin sheaths of normal length and thickness are regenerated during this time. Interestingly, we find that axons grow significantly in caliber during this period of remyelination. This suggests the possibility that the active growth of axons may stimulate the regeneration of myelin sheaths of normal dimensions.

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A novel model of demyelination and remyelination in a GFP-transgenic zebrafish

Cited by 24 publications

References 34 publications

Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

Analysis of myelinated axon formation in zebrafish

Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber

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