Abstract

Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node (RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para- and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter; therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.

Highlights

  • Microglia, the brain resident cells that can sense pathological tissue alterations, are believed to be quiescent in physiological circumstances[1–2]

  • In combination of labeling para- or inter-nodal domains by pertained markers, we showed in this work the potential contacts of microglia pseudopodia with the Ranvier’s node (RN) and with para- and inter-nodal myelin sheathes in the rat corpus callosum (CC)

  • To the best of our knowledge, the findings presented here, demonstrate for the first time that microglia pseudopodia directly contact with RN and paranodal or internodal myelin sheath in healthy young adult central nerve system (CNS) white matter

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Summary

Introduction

The brain resident cells that can sense pathological tissue alterations, are believed to be quiescent in physiological circumstances[1–2]. In recent decades, microglia are found to be more than passive responders. They show high levels of activity with their pseudopodia exploring the surrounding environment, which is known as “dynamic surveillance of brain parenchyma”[3–5]. One of the newly observed physiological functions of microglia is their involvement in synaptic stripping or pruning[4–5]. Under a twophoton live-image microscope, fine microglia pseudopodia are viewed to extend to pre- and post-synaptic structures at a certain rate. Direct contacts of labeled microglia processes onto synapses and/or engulfed post-synaptic protein in microglia cytoplasm have been envisioned under the electron microscope[4–6]. Microglia are responsible for removing the less-used synapses[5,7]

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