1. Progressive postnatal motoneuron loss in mice lacking GDF-15
- Author
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Gerald Bendner, Klaus Unsicker, Patricia M. Rusu, Amy L. Altick, Francesca Diella, Jens Strelau, Christopher S. von Bartheld, Adam Strzelczyk, Michael Sendtner, Stefan Wiese, and Rüdiger Klein
- Subjects
Growth Differentiation Factor 15 ,Sympathetic Nervous System ,Sensory Receptor Cells ,Cell Survival ,Mice, Transgenic ,Ciliary neurotrophic factor ,Article ,Midbrain ,Mice ,Neurotrophic factors ,Ganglia, Spinal ,medicine ,Animals ,Ciliary Neurotrophic Factor ,Trigeminal Nerve ,Muscle, Skeletal ,Cells, Cultured ,Trigeminal nerve ,Motor Neurons ,Neurons ,biology ,Cell Death ,General Neuroscience ,Spinal cord ,Sciatic Nerve ,Mice, Inbred C57BL ,Facial Nerve ,medicine.anatomical_structure ,nervous system ,Spinal Cord ,Motor Skills ,embryonic structures ,biology.protein ,Sciatic nerve ,Schwann Cells ,Neuroscience ,Neurotrophin - Abstract
Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-β 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 ∼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.
- Published
- 2009