title: Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury.
abstract: The adhesion molecule L1 is one of the few adhesion molecules known to be beneficial for repair processes in the adult central nervous system of vertebrates by promoting axonal growth and neuronal survival. In the peripheral nervous system, L1 is up-regulated by myelination-competent Schwann cells and regenerating axons after nerve damage but its functional role has remained unknown. Here we tested the hypothesis that L1 is, as in the central nervous system, beneficial for nerve regeneration in the peripheral nervous system by performing combined functional and histological analyses of adult L1-deficient mice (L1y/-) and wild-type (L1y/+) littermates. Contrary to our hypothesis, quantitative video-based motion analysis revealed better locomotor recovery in L1y/- than in L1y/+ mice at 4-12 weeks after transection and surgical repair of the femoral nerve. Motoneuron regeneration in L1y/- mice was also enhanced as indicated by attenuated post-traumatic loss of motoneurons, enhanced precision of motor reinnervation, larger cell bodies of regenerated motoneurons and diminished loss of inhibitory synaptic input to motoneurons. In search of mechanisms underlying the observed effects, we analysed peripheral nerves at short time-periods (3-14 days) after transection and found that Schwann cell proliferation is strongly augmented in L1y/- versus L1y/+ mice. L1-deficient Schwann cells showed increased proliferation than wild-type Schwann cells, both in vivo and in vitro. These findings suggest a novel role for L1 in nerve regeneration. We propose that L1 negatively regulates Schwann cell proliferation after nerve damage, which in turn restricts functional recovery by limiting the trophic support for regenerating motoneurons.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Hamburg, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.forename: Doychin N
authors.initials: DN
authors.lastname: Angelov
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D005267:Femoral Nerve / Q000293:injuries / Q000502:physiology / Q000601:surgery; D007794:Lameness, Animal / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency / Q000502:physiology*; D017933:Peripheral Nervous System / Q000293:injuries* / Q000502:physiology; D017729:Presynaptic Terminals / Q000473:pathology; D020127:Recovery of Function; D012583:Schwann Cells / Q000473:pathology*; D013569:Synapses / Q000502:physiology
chemical_list: D039842:Neural Cell Adhesion Molecule L1