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Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury
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Progressive postnatal motoneuron loss in mice lacking GDF-15.

Jens Strelau1, Adam Strzelczyk, Patricia Rusu

  • 1Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|October 30, 2009
PubMed
Summary

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Growth/differentiation factor-15 (GDF-15) deficiency causes significant motor neuron loss and impaired motor skills in mice. GDF-15 is identified as a novel trophic factor crucial for motor and sensory neuron survival.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Growth/differentiation factor-15 (GDF-15) is a TGF-beta superfamily member with known neurotrophic roles.
  • Its specific functions in the peripheral nervous system are not fully understood.

Purpose of the Study:

  • To investigate the role of GDF-15 in the survival and maintenance of motor and sensory neurons.
  • To determine if GDF-15 acts as a novel neurotrophic factor.

Main Methods:

  • Generation and analysis of GDF-15-deficient mice.
  • Assessment of motoneuron and sensory neuron populations.
  • Evaluation of motor function using rotarod tests.
  • Investigation of GDF-15 expression and transport in peripheral nerves.
  • Analysis of neuronal survival in vitro and in vivo.

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Main Results:

  • GDF-15-deficient mice showed progressive loss of spinal, facial, and trigeminal motoneurons (up to 20%).
  • Sensory neurons in dorsal root ganglia were also reduced by 20%, while sympathetic neurons remained unaffected.
  • Motor axon loss and impaired rotarod performance were observed in deficient mice.
  • GDF-15 is expressed by Schwann cells and retrogradely transported along axons.
  • GDF-15 promoted survival of axotomized facial neurons and cultured neurons.

Conclusions:

  • GDF-15 is essential for the postnatal survival of motor and sensory neurons.
  • GDF-15 functions as a novel neurotrophic factor for motor and sensory neurons.
  • Its role is distinct from other known neurotrophic factors like CNTF.