Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood
Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood
Neuregulin-1 (NRG1) plays a crucial role in axoglial signaling during the development of the peripheral nervous system, but its importance in adulthood after peripheral nerve injury remains unclear. We used single-neuron labeling with inducible Cre-mediated knock-out animals, which enabled visualization of a subset of adult myelinated sensory and motoneurons neurons in whichNrg1was inducibly mutated by tamoxifen treatment. In uninjured mice, NRG1-deficient axons and the associated myelin sheath were normal, and the neuromuscular junction demonstrated normal apposition of presynaptic and postsynaptic components. After sciatic nerve crush, NRG1 ablation resulted in severe defects in remyelination: axons were either hypomyelinated or had no myelin sheath. NRG1-deficient axons were also found to regenerate at a slower rate. After nerve injury, the neuromuscular junction was reinnervated, but excess terminal sprouting was observed. Juxtacrine Neuregulin-1 signaling is therefore dispensable for maintenance of the myelin sheath in adult animals but has a key role in reparative processes after nerve injury.
- King's College London United Kingdom
- University of Oxford United Kingdom
- Kings College London, University of London United Kingdom
- Wolfson Centre for Age-Related Diseases United Kingdom
Mice, Knockout, 570, Aging, Neuregulin-1, Neuromuscular Junction, 610, Mice, Transgenic, Nerve Fibers, Myelinated, Axons, Nerve Regeneration, Mice, Inbred C57BL, Mice, Animals, Sciatic Neuropathy, Function and Dysfunction of the Nervous System, Myelin Sheath
Mice, Knockout, 570, Aging, Neuregulin-1, Neuromuscular Junction, 610, Mice, Transgenic, Nerve Fibers, Myelinated, Axons, Nerve Regeneration, Mice, Inbred C57BL, Mice, Animals, Sciatic Neuropathy, Function and Dysfunction of the Nervous System, Myelin Sheath
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