title: Growth/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration.
abstract: Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor beta (TGF-β) superfamily. It is widely distributed in the nervous system, where it has been shown to play an important role in neuronal maintenance. The present study investigates the role of endogenous GDF-15 in sciatic nerve (SN) lesions using wild-type (WT) and GDF-15 knock-out (KO) mice. SN of 5-6-month-old mice were crushed or transected. Dorsal root ganglia (DRG) and nerve tissue were analyzed at different time points from 6 h to 9 weeks post-lesion. Both crush and transection induced GDF-15 mRNA and protein in the distal portion of the nerve, with a peak at day 7. DRG neuron death did not significantly differ between the genotypes; similarly, remyelination of regenerating axons was not affected by the genotype. Alternative macrophage activation and macrophage recruitment were more pronounced in the KO nerve. Protrusion speed of axons was similar in the two genotypes but WT axons showed better maturation, as indicated by larger caliber at 9 weeks. Furthermore, the regenerated WT nerve showed better performance in the electromyography test, indicating better functional recovery. We conclude that endogenous GDF-15 is beneficial for axon regeneration following SN crush.
authors.affiliation: Institute of Anatomy & Cell Biology, Department of Molecular Embryology, University of Freiburg, Albertstr. 17, D-79104, Freiburg, Germany.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory for Molecular Neurobiology, Clinic of Neurology, Heinrich-Heine-University, Moorenstr. 5, D-40225, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Krebbers
authors.affiliation: Institute of Anatomy & Cell Biology, Department of Molecular Embryology, University of Freiburg, Albertstr. 17, D-79104, Freiburg, Germany.
authors.forename: Petar
authors.initials: P
authors.lastname: Charalambous
authors.affiliation: Institute of Anatomy & Cell Biology, Department of Molecular Embryology, University of Freiburg, Albertstr. 17, D-79104, Freiburg, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Albertstr. 19A, D-79104, Freiburg, Germany.
authors.forename: Venissa
authors.initials: V
authors.lastname: Machado
authors.affiliation: Institute of Anatomy & Cell Biology, Department of Molecular Embryology, University of Freiburg, Albertstr. 17, D-79104, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.affiliation: Laboratory for Molecular Neurobiology, Clinic of Neurology, Heinrich-Heine-University, Moorenstr. 5, D-40225, Düsseldorf, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bosse
authors.affiliation: Laboratory for Molecular Neurobiology, Clinic of Neurology, Heinrich-Heine-University, Moorenstr. 5, D-40225, Düsseldorf, Germany.
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Müller
authors.affiliation: Institute of Anatomy & Cell Biology, Department of Molecular Embryology, University of Freiburg, Albertstr. 17, D-79104, Freiburg, Germany. ku39@anat.uni-freiburg.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009409:Nerve Crush / Q000379:methods; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D012584:Sciatic Nerve / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D016212:Transforming Growth Factor beta
keywords: Axon generation; GDF-15; Growth/differentiation factor-15; Sciatic nerve lesion; TGF-β