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Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury
Published on: February 23, 2015
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.
Abstract:
Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-beta superfamily with prominent neurotrophic effects on midbrain dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit reaches a approximately 20% maximum at 6 months and is accompanied by losses of motor axons and significant impairment of rotarod skills. Similarly, sensory neurons in dorsal root ganglia (L4, L5) are reduced by 20%, whereas sympathetic neurons are not affected. GDF-15 is expressed and secreted by Schwann cells, retrogradely transported along adult sciatic nerve axons, and promotes survival of axotomized facial neurons as well as cultured motor, sensory, and sympathetic neurons. Despite striking similarities in the GDF-15 and CNTF knock-out phenotypes, expression levels of CNTF and other neurotrophic factors in the sciatic nerve were unaltered suggesting that GDF-15 is a genuine novel trophic factor for motor and sensory neurons.
Insights
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.
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.
