CNS Live Imaging Reveals a New Mechanism of Myelination: The Liquid Croissant Model (P02.065)

Abstract

Objective: Even though the current model of myelination has been recognized as insufficient, CNS myelin formation has not yet been investigated in real-time with the requisite technique and resolution. Using confocal live microscopy, our study intends to provide further insight into the mechanism of myelination of the central nervous system. Background Based on electron microscopic findings more than half a century ago, the current model of myelination describes all myelin membranes to run in parallel with the longitudinal axis of the axon and to form a smooth surface, reminiscent of a rolled up carpet. However, different studies in the past demonstrated a distinct myelin morphology with an uneven myelin surface contour that challenges the established concept. Design/Methods: We therefore traced myelin growth in murine organotypic cerebellar slice cultures using high-resolution confocal live imaging, light and electron microscopy and assessed myelin morphology in young and adult mice by confocal microscopy. Results: Our data verify that the myelin surface is indeed not smooth but runs in a bidirectional, regularly spaced coil along the axon in both young and adult mice. Time-lapse imaging revealed that the growth of coiled myelin turns emerges during myelin formation. Conclusions: We therefore propose the liquid croissant model as a new concept of myelination that overcomes not only some of the incongruences of previous myelination theories, but potentially also explains the development of certain myelin pathologies observed in remyelination and axonopathies. Supported by: Swiss Multiple Sclerosis Society, Swiss National Science Foundation, 3R Research Foundation, University of Zurich, Research Commission of the Medical Faculty of the Heinrich-Heine-University Dusseldorf. Disclosure: Dr. Goebels has received personal compensation for activities with Biogen Idec, Bayer Pharmaceuticals Corporation, Merck Serono, Novartis and Teva Neuroscience as a speaker and participant on advisory boards. Dr. Sobottka has nothing to disclose. Dr. Kaech has nothing to disclose. Dr. Becher has nothing to disclose. Dr. Ziegler has nothing to disclose.