Progressive postnatal motoneuron loss in mice lacking GDF-15

Jens Strelau, Adam Strzelczyk, Patricia Rusu, Gerald Bendner, Stefan Wiese, Francesca Diella, Amy L. Altick, Christopher S. Von Bartheld, Rüdiger Klein, Michael Sendtner, Klaus Unsicker

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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%maximumat 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.

Original languageEnglish
Pages (from-to)13640-13648
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number43
DOIs
Publication statusPublished - 28 Oct 2009
Externally publishedYes

Cite this

Strelau, J., Strzelczyk, A., Rusu, P., Bendner, G., Wiese, S., Diella, F., Altick, A. L., Von Bartheld, C. S., Klein, R., Sendtner, M., & Unsicker, K. (2009). Progressive postnatal motoneuron loss in mice lacking GDF-15. Journal of Neuroscience, 29(43), 13640-13648. https://doi.org/10.1523/JNEUROSCI.1133-09.2009