title: Remyelination reporter reveals prolonged refinement of spontaneously regenerated myelin.
abstract: Neurological diseases and trauma often cause demyelination, resulting in the disruption of axonal function and integrity. Endogenous remyelination promotes recovery, but the process is not well understood because no method exists to definitively distinguish regenerated from preexisting myelin. To date, remyelinated segments have been defined as anything abnormally short and thin, without empirical data to corroborate these morphological assumptions. To definitively identify regenerated myelin, we used a transgenic mouse with an inducible membrane-bound reporter and targeted Cre recombinase expression to a subset of glial progenitor cells after spinal cord injury, yielding remarkably clear visualization of spontaneously regenerated myelin in vivo. Early after injury, the mean length of sheaths regenerated by Schwann cells and oligodendrocytes (OLs) was significantly shorter than control, uninjured myelin, confirming past assumptions. However, OL-regenerated sheaths elongated progressively over 6 mo to approach control values. Moreover, OL-regenerated myelin thickness was not significantly different from control myelin at most time points after injury. Thus, many newly formed OL sheaths were neither thinner nor shorter than control myelin, vitiating accepted dogmas of what constitutes regenerated myelin. We conclude that remyelination, once thought to be static, is dynamic and elongates independently of axonal growth, in contrast to stretch-based mechanisms proposed in development. Further, without clear identification, past assessments have underestimated the extent and quality of regenerated myelin.
authors: Department of Neurological Surgery and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors: Berit E
authors: BE
authors: Powers
authors: Drew L
authors: DL
authors: Sellers
authors: Emilie A
authors: EA
authors: Lovelett
authors: Willy
authors: W
authors: Cheung
authors: Sheida P
authors: SP
authors: Aalami
authors: Nikolai
authors: N
authors: Zapertov
authors: Don O
authors: DO
authors: Maris
authors: Philip J
authors: PJ
authors: Horner
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
chemical_list: D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins