title: Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination.
abstract: As lysosomal hydrolysis has long been suggested to be responsible for myelin clearance after peripheral nerve injury, in this study, we investigated the possible role of autophagolysosome formation in myelin phagocytosis by Schwann cells and its final contribution to nerve regeneration. We found that the canonical formation of autophagolysosomes was induced in demyelinating Schwann cells after injury, and the inhibition of autophagy via Schwann cell-specific knockout of the atg7 gene or pharmacological intervention of lysosomal function caused a significant delay in myelin clearance. However, Schwann cell dedifferentiation, as demonstrated by extracellular signal-regulated kinase activation and c-Jun induction, and redifferentiation were not significantly affected, and thus the entire repair program progressed normally in atg7 knockout mice. Finally, autophagic Schwann cells were also found during segmental demyelination in a mouse model of inflammatory peripheral neuropathy. Together, our findings suggest that autophagy is the self-myelin destruction mechanism of Schwann cells, but mechanistically, it is a process distinct from Schwann cell plasticity for nerve repair.
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Dong-a University, Busan, Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Neurology, College of Medicine, Dong-a University, Busan, Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Dong-a University, Busan, Korea.
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000209:etiology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D008247:Lysosomes / Q000473:pathology; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D012583:Schwann Cells / Q000648:ultrastructure; D012585:Sciatica / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000150:complications* / Q000235:genetics / Q000473:pathology*
chemical_list: C502661:Atg7 protein, mouse; D004791:Enzyme Inhibitors; D018942:Macrolides; C040929:bafilomycin A1; D000071193:Autophagy-Related Protein 7
keywords: autophagy; conditional knockout; dedifferentiation; inflammatory neuropathy; injury; lysosome