Schmidt-Lanterman incisures in the Schwann cell and their role for peripheral nerve regeneration

Abstract

Schmidt-Lanterman incisures (SLIs) are cytoplasmic channels within compact peripheral myelin, yet their formation and functional relevance in health and disease remain incompletely understood. This study investigates SLI development, their regulation across the lifespan, and their role in neuropathy and nerve regeneration. Using immunofluorescence and high-pressure freezing electron microscopy of developing murine sciatic nerves, we show that SLIs arise early during myelin formation. During development, SLI number increases in parallel with internodal elongation and remains stable in adulthood and aging, indicating an essential role in Schwann cell maturation and myelin maintenance. In mouse models of PMP22-associated neuropathies (CMT1A and HNPP), SLI number is altered in a dosage-dependent manner: increased in PMP22-duplication and transiently reduced during early development in PMP22-deletion. Similarly, sural nerve biopsies from patients with demyelinating neuropathy reveal increased SLI numbers, particularly in short internodes, suggesting a compensatory function in disease. Following sciatic nerve crush injury, mice with reduced SLI numbers (VCLcKO) exhibit delayed motor recovery and fail to upregulate SLIs, in contrast to wildtype controls. These findings support a critical role of SLIs in preserving nerve function and promoting regeneration, potentially by facilitating axo-glial communication and metabolic support. Together, this work identifies SLIs as dynamic and regulated structures essential for peripheral nerve development, maintenance, and repair, highlighting their potential as targets for therapeutic strategies to enhance nerve regeneration.10000-01-01Diese Dateien sind bis zum Abschluß der Staatsexamensprüfung gesperrt.These files are not accessible until the state exam has been completed