The development of a novel demyelination zebrafish model to be used for high-throughput drug screening of pro-myelinating compounds in multiple sclerosis
Author(s): ,
A. McGown
Neuroscience, University of Sheffield, Sheffield, United Kingdom
B. Sharrack
Neuroscience, University of Sheffield, Sheffield, United Kingdom
T. Ramesh
Neuroscience, University of Sheffield, Sheffield, United Kingdom
ECTRIMS Online Library. McGown A. Oct 9, 2015; 116013; 1543
Alexander McGown
Alexander McGown
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Abstract: P857

Type: Poster

Abstract Category: Experimental models

Background: Current animal models of multiple sclerosis (MS) focus on inducing neuroinflammation or causing focal demyelination. Lysolecithin is a commonly used toxin which induces focal demyelination in rodent models. However, such models are expensive and have low throughput in therapeutic testing. There is a need to identify new models which have high throughput to improve therapeutic discovery in MS. Zebrafish are emerging as an excellent tool to help developing a better understanding of various neurodegenerative disorders. The rapid development, characterised central nervous system, transgenic models and large numbers of offspring lend themselves well to drug discovery. Zebrafish models currently exist for many neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis.

Objective: Here we describe the development of a rapid demyelination/remyelination zebrafish model, which has the potential to be used in the high-throughput screening of therapeutic compounds which promote remyelination.

Methods: Oligodendrocytes are the key myelinating cell in the zebrafish central nervous system. Demyelination was induced by injection of a lysolecithin solution directly into the CNS of the zebrafish at day 4.

Results: Oligodendrocyte cell processes were vastly reduced 24 hours after toxin exposure and continue to be significantly reduced for 4 days. This was not due to oligodendrocyte toxicity as no decrease in cell body number was seen after lysolecithin treatment. Myelination was significant reduced in the optic tectum 48 hours post injection. Neuroinflammation, a key pathogenic pathway in MS, was detectable 3 days post injection, with a significant increase in leukocytes seen within the white matter tracts. Neuroinflammation is a continuing process that continues throughout the remyelination process. Recovery of oligodendrocyte processes was seen by 4 days post injection, and myelin returned to control levels by 6 days post injection highlighting the usefulness of this model as a rapid tool for investigating the pathways involved in demyelination/remyelination.

Conclusion: We describe a robust, rapid and reproducible model of demyelination and remyelination that models two of the key pathological characteristics of MS (neuroinflammation and demyelination). Future work on this model is underway to optimise and validate it as a screen tool for assesing pro myelinating therapeutic compounds.


Alexander McGown: Nothing to disclose
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