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Schwann cell dedifferentiation‐associated demyelination leads to exocytotic myelin clearance in inflammatory segmental demyelination
Author(s) -
Jang So Young,
Yoon ByeolA,
Shin Yoon Kyung,
Yun Seoug Hoon,
Jo Young Rae,
Choi Yun Young,
Ahn Meejung,
Shin Taekyun,
Park Joo In,
Kim Jong Kuk,
Park Hwan Tae
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23200
Subject(s) - myelin , wallerian degeneration , microbiology and biotechnology , biology , schwann cell , neuroscience , central nervous system
Schwann cells (SCs), which form the peripheral myelin sheath, have the unique ability to dedifferentiate and to destroy the myelin sheath under various demyelination conditions. During SC dedifferentiation‐associated demyelination (SAD) in Wallerian degeneration (WD) after axonal injury, SCs exhibit myelin and junctional instability, down‐regulation of myelin gene expression and autophagic myelin breakdown. However, in inflammatory demyelinating neuropathy (IDN), it is still unclear how SCs react and contribute to segmental demyelination before myelin scavengers, macrophages, are activated for phagocytotic myelin digestion. Here, we compared the initial SC demyelination mechanism of IDN to that of WD using microarray and histochemical analyses and found that SCs in IDN exhibited several typical characteristics of SAD, including actin‐associated E‐cadherin destruction, without obvious axonal degeneration. However, autophagolysosome activation in SAD did not appear to be involved in direct myelin lipid digestion by SCs but was required for the separation of SC body from destabilized myelin sheath in IDN. Thus, lysosome inhibition in SCs suppressed segmental demyelination by preventing the exocytotic myelin clearance of SCs. In addition, we found that myelin rejection, which might also require the separation of SC cytoplasm from destabilized myelin sheath, was delayed in SC‐specific Atg7 knockout mice in WD, suggesting that autophagolysosome‐dependent exocytotic myelin clearance by SCs in IDN and WD is a shared mechanism. Finally, autophagolysosome activation in SAD was mechanistically dissociated with the junctional destruction in both IDN and WD. Thus, our findings indicate that SAD could be a common myelin clearance mechanism of SCs in various demyelinating conditions.