Neuroprotection, Regeneration and/or Remyelination Poster Presentation

P0778 - IL-10 promotes myelin repair in an ex vivo model of remyelination and microRNA signatures of ex vivo remyelination (ID 1761)

Speakers
  • C. Duffy
Authors
  • C. Duffy
  • C. McCoy
  • M. Muñoz San Martín
Presentation Number
P0778
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination

Abstract

Background

Multiple sclerosis is an autoimmune disease characterized by peripheral immune infiltration of the CNS and subsequent demyelination of axons, leading in turn to neuron damage and death. This damage can be repaired, however, via a process of remyelination of previous damaged neurons. The cytokine IL-10 has been shown to promote a micro-environment conducive to myelin repair, however the underlying mechanism remains poorly understood. MicroRNAs are known to play a central role in regulating remyelination, and represent a potential means by which IL-10 may influence remyelination. For example, we have previously shown that IL-10 can inhibit the microRNA miR-155 and may influence this process.

Objectives

To investigate the role of IL-10 in promoting remyelination and to profile global miRNA expression in an ex vivo model of remyelination.

Methods

Remyelination was modelled ex vivo by application of the demyelinating drug lysolecithin to cultured organotypic cerebellum and brain stem cultures, then treated with LPS and/or IL-10. The extent of remyelination was assessed using immunofluorescent microscopy and Image J analysis. Additionally, we used a custom designed OpenArray to assess microRNA expression in the demyelination and remyelination phases of this model. The expression of several microRNAs of interest were verified using RT-PCR.

Results

Demyelinated slices treated with a combination of LPS and IL-10 show greater remyelination than slices left untreated or that received only one of these stimuli. Moreover, brain slices obtained from miR-155 knockout mice displayed greater basal levels of remyelination, absent of any stimuli and suggest a mechanism by which IL-10 may mediate this effect. Additionally, from the OpenArray, we identified altered expression of several microRNAs across the phases of demyelination and remyelination in the brain slice model. One such microRNA, miR-448, was upregulated at the remyelination phase, and we further illustrate that several targets of this microRNAs are impacted.

Conclusions

IL-10 supports remyelination when combined with the inflammatory stimulus LPS, and possibly may work via miR-155 to promote repair. Several other miRNAs like miR-448 are also modulated during remyelination and may be worth exploring further.

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