Strelau Jens, Strzelczyk Adam, Rusu Patricia, Bendner Gerald, Wiese Stefan, Diella Francesca, Altick Amy L, von Bartheld Christopher S, Klein Rüdiger, Sendtner Michael, Unsicker Klaus
Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany.
J Neurosci. 2009 Oct 28;29(43):13640-8. doi: 10.1523/JNEUROSCI.1133-09.2009.
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.
生长/分化因子-15（GDF-15）是转化生长因子-β（TGF-β）超家族中广泛表达的远亲成员，对中脑多巴胺能神经元具有显著的神经营养作用。我们在此表明，GDF-15基因缺陷小鼠出生后脊髓、面部和三叉神经运动神经元逐渐丧失。这种缺陷在6个月时达到约20%的最大值，并伴有运动轴突的丧失和转棒技能的显著受损。同样，背根神经节（L4、L5）中的感觉神经元减少了20%，而交感神经元未受影响。GDF-15由雪旺细胞表达和分泌，沿成年坐骨神经轴突逆行运输，并促进切断轴突的面部神经元以及培养的运动、感觉和交感神经元的存活。尽管GDF-15和睫状神经营养因子（CNTF）基因敲除表型有惊人的相似之处，但坐骨神经中CNTF和其他神经营养因子的表达水平未改变，这表明GDF-15是运动和感觉神经元真正的新型营养因子。
