Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood

Florence R. Fricker; Natalia Lago; Sharmili Balarajah; Christoforos Tsantoulas; Shamil Tanna; Ning Zhu; Samaher K. Fageiry; Mark Jenkins; Alistair N. Garratt; Carmen Birchmeier; David L. H. Bennett

doi:10.1523/JNEUROSCI.2568-10.2011

Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood

Florence R. Fricker, Natalia Lago, Sharmili Balarajah, Christoforos Tsantoulas, Shamil Tanna, Ning Zhu, Samaher K. Fageiry, Mark Jenkins, Alistair N. Garratt, Carmen Birchmeier, David L. H. Bennett

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119 Citations (Scopus)

Abstract

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 which Nrg1 was 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.

Original language	English
Pages (from-to)	3225 - 3233
Number of pages	9
Journal	Journal of Neuroscience
Volume	31
Issue number	9
DOIs	https://doi.org/10.1523/JNEUROSCI.2568-10.2011
Publication status	Published - 2 Mar 2011

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@article{1333e00ad3674be3894b5d532c2931b8,

title = "Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood",

abstract = "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 which Nrg1 was 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.",

author = "Fricker, {Florence R.} and Natalia Lago and Sharmili Balarajah and Christoforos Tsantoulas and Shamil Tanna and Ning Zhu and Fageiry, {Samaher K.} and Mark Jenkins and Garratt, {Alistair N.} and Carmen Birchmeier and Bennett, {David L. H.}",

year = "2011",

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doi = "10.1523/JNEUROSCI.2568-10.2011",

language = "English",

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pages = "3225 -- 3233",

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T1 - Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood

AU - Fricker, Florence R.

AU - Lago, Natalia

AU - Balarajah, Sharmili

AU - Tsantoulas, Christoforos

AU - Tanna, Shamil

AU - Zhu, Ning

AU - Fageiry, Samaher K.

AU - Jenkins, Mark

AU - Garratt, Alistair N.

AU - Birchmeier, Carmen

AU - Bennett, David L. H.

PY - 2011/3/2

Y1 - 2011/3/2

N2 - 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 which Nrg1 was 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.

AB - 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 which Nrg1 was 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.

U2 - 10.1523/JNEUROSCI.2568-10.2011

DO - 10.1523/JNEUROSCI.2568-10.2011

M3 - Article

SN - 1529-2401

VL - 31

SP - 3225

EP - 3233

JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 9

ER -

Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood

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