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Translational Neurodegeneration
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Open Access 01-12-2017 | Research

Elevated axonal membrane permeability and its correlation with motor deficits in an animal model of multiple sclerosis

Authors: Gary Leung, Melissa Tully, Jonathan Tang, Shengxi Wu, Riyi Shi

Published in: Translational Neurodegeneration | Issue 1/2017

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Abstract

Background

It is increasingly clear that in addition to myelin disruption, axonal degeneration may also represent a key pathology in multiple sclerosis (MS). Hence, elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology, but also elucidate additional therapeutic targets. The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice.

Methods

Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud’s adjuvant emulsion, followed by two intraperitoneal injections of pertussis toxin. Behavioral assessment was performed using a 5-point scale. Horseradish Peroxidase Exclusion test was used to quantify the disruption of axonal membrane. Polyethylene glycol was prepared as a 30% (w/v) solution in phosphate buffered saline and injected intraperitoneally.

Results

We have found evidence of axonal membrane disruption in EAE mice when symptoms peak and to a lesser degree, in the pre-symptomatic stage of EAE mice. Furthermore, polyethylene glycol (PEG), a known membrane fusogen, significantly reduces axonal membrane disruption in EAE mice. Such PEG-mediated membrane repair was accompanied by significant amelioration of behavioral deficits, including a delay in the emergence of motor deficits, a delay of the emergence of peak symptom, and a reduction in the severity of peak symptom.

Conclusions

The current study is the first indication that axonal membrane disruption may be an important part of the pathology in EAE mice and may underlies behavioral deficits. Our study also presents the initial observation that PEG may be a therapeutic agent that can repair axolemma, arrest axonal degeneration and reduce motor deficits in EAE mice.
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Metadata
Title
Elevated axonal membrane permeability and its correlation with motor deficits in an animal model of multiple sclerosis
Authors
Gary Leung
Melissa Tully
Jonathan Tang
Shengxi Wu
Riyi Shi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2017
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-017-0075-7

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