TY - JOUR
T1 - Progressive postnatal motoneuron loss in mice lacking GDF-15
AU - Strelau, Jens
AU - Strzelczyk, Adam
AU - Rusu, Patricia
AU - Bendner, Gerald
AU - Wiese, Stefan
AU - Diella, Francesca
AU - Altick, Amy L.
AU - Von Bartheld, Christopher S.
AU - Klein, Rüdiger
AU - Sendtner, Michael
AU - Unsicker, Klaus
PY - 2009/10/28
Y1 - 2009/10/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70350528733&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1133-09.2009
DO - 10.1523/JNEUROSCI.1133-09.2009
M3 - Article
C2 - 19864576
AN - SCOPUS:70350528733
SN - 0270-6474
VL - 29
SP - 13640
EP - 13648
JO - The Journal of Neuroscience
JF - The Journal of Neuroscience
IS - 43
ER -