Cellular and Molecular Mechanisms Underpinning Macrophage Activation during Remyelination.

Amy F Lloyd,Veronique E Miron

doi:10.3389/fcell.2016.00060

Abstract

Remyelination is an example of central nervous system (CNS) regeneration, whereby myelin is restored around demyelinated axons, re-establishing saltatory conduction and trophic/metabolic support. In progressive multiple sclerosis, remyelination is limited or fails altogether which is considered to contribute to axonal damage/loss and consequent disability. Macrophages have critical roles in both CNS damage and regeneration, such as remyelination. This diverse range in functions reflects the ability of macrophages to acquire tissue microenvironment-specific activation states. This activation is dynamically regulated during efficient regeneration, with a switch from pro-inflammatory to inflammation-resolution/pro-regenerative phenotypes. Although, some molecules and pathways have been implicated in the dynamic activation of macrophages, such as NFκB, the cellular and molecular mechanisms underpinning plasticity of macrophage activation are unclear. Identifying mechanisms regulating macrophage activation to pro-regenerative phenotypes may lead to novel therapeutic strategies to promote remyelination in multiple sclerosis.

Highlights

A prime example of regeneration in the central nervous system (CNS) is remyelination, whereby following demyelination, myelin is regenerated around axons allowing recovery of saltatory electrical impulse conduction and metabolic/trophic support
Remyelination is limited or fails altogether in the progressive phase of the autoimmune disease multiple sclerosis (MS), which is considered to contribute to the axonal damage and loss that correlates to sensory, motor and cognitive decline
These findings indicate that timed coordination of particular macrophage phenotypes and functions are essential for efficient remyelination, the cues dictating their activation and phenotypic switching remain poorly understood

Summary

Introduction

A prime example of regeneration in the central nervous system (CNS) is remyelination, whereby following demyelination, myelin is regenerated around axons allowing recovery of saltatory electrical impulse conduction and metabolic/trophic support. IL-4 injection had a pro-regenerative effect in the immune-mediated demyelination mouse model experimental autoimmune encephalitis (EAE), where it increased oligodendrogenesis in the spinal cord, suggesting potential involvement of microglia/macrophages in remyelination.

Results

Conclusion