Sunday, 30 June 2013

Remyelinating fish

Epub: Chung et al. Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS. Mol Cells. 2013 Jun 25.

Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis. In spite of numerous studies aimed at understanding the remyelination process, many questions still remain unanswered. Therefore, to study remyelination mechanisms in vivo, a demyelination animal model was generated using a transgenic zebrafish system in which oligodendrocytes are conditionally ablated in the larval and adult CNS. In this transgenic system, bacterial nitroreductase enzyme (NTR), which converts the prodrug metronidazole (Mtz) into a cytotoxic DNA cross-linking agent, is expressed in oligodendrocyte lineage cells under the control of the mbp and sox10 promoter. Exposure of transgenic zebrafish to Mtz-containing media resulted in rapid ablation of oligodendrocytes and CNS demyelination within 48 h, but removal of Mtz medium led to efficient remyelination of the demyelinated CNS within 7 days. In addition, the demyelination and remyelination processes could be easily observed in living transgenic zebrafish by detecting the fluorescent protein, mCherry, indicating that this transgenic system can be used as a valuable animal model to study the remyelination process in vivo, and to conduct high-throughput primary screens for new drugs that facilitate remyelination.


Zebrafish as increasing being used as it means use of less animals in research. The larval forms are transparent so you see things you can label structures with green fluorescence protein from Jellyfish or mCherry a monomeric red fluorescent protein from disc coral.



This study has devised a novel way to demyelinate axons by having an oligodendrocyte toxin that can be switched on and off. As is common in mammals the default pathway is rapid repair. This system may be used to study repair. 

It is a shame that many drugs that get into the brain are like brick dust when it comes to dissolving in water, but maybe there is space for a new FishDoctor on the blog?

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