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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11054

Title: C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts
Authors: Boato, Francesco
Huelsenbeck, Stefanie C.
Hofmann, Fred
Grosse, Gisela
Djalali, Susann
Klimaschewski, Lars
Auer, Maria
Just, Ingo
Ahnert-Hilger, Gudrun
Hoeltje, Markus
Issue Date: 2010
Citation: JOURNAL OF CELL SCIENCE, 123 (10). p. 1652-1662
Abstract: Functional recovery and regeneration of corticospinal tract (CST) fibers following spinal cord injury by compression or dorsal hemisection in mice was monitored after application of the enzyme-deficient Clostridium botulinum C3-protein-derived 29-amino-acid fragment C3bot(154-182). This peptide significantly improved locomotor restoration in both injury models as assessed by the open-field Basso Mouse Scale for locomotion test and Rotarod treadmill experiments. These data were supported by tracing studies showing an enhanced regenerative growth of CST fibers in treated animals as visualized by anterograde tracing. Additionally, C3bot(154-182) stimulated regenerative growth of raphespinal fibers and improved serotonergic input to lumbar alpha-motoneurons. These in vivo data were confirmed by in vitro data, showing an enhanced axon outgrowth of alpha-motoneurons and hippocampal neurons cultivated on normal or growth-inhibitory substrates after application of C3bot(154-182). The observed effects were probably caused by a non-enzymatic downregulation of active RhoA by the C3 peptide as indicated by pull-down experiments. By contrast, C3bot(154-182) did not induce neurite outgrowth in primary cultures of dorsal root ganglion cells. In conclusion, C3bot(154-182) represents a novel, promising tool to foster axonal protection and/or repair, as well as functional recovery after traumatic CNS injury.
Notes: [Boato, Francesco; Hendrix, Sven; Hoeltje, Markus] Charite, Ctr Anat, Inst Cell Biol & Neurobiol, D-10117 Berlin, Germany. [Hendrix, Sven] Hasselt Univ, Dept Morphol, B-3590 Diepenbeek, Belgium. [Hendrix, Sven] Hasselt Univ, Inst Biomed, B-3590 Diepenbeek, Belgium. [Huelsenbeck, Stefanie C.; Hofmann, Fred; Just, Ingo] Hannover Med Sch MHH, Inst Toxicol, D-30625 Hannover, Germany. [Klimaschewski, Lars; Auer, Maria] Innsbruck Med Univ, Dept Anat Histol & Embryol, Div Neuroanat, A-6020 Innsbruck, Austria. markus.hoeltje@charite.de
URI: http://hdl.handle.net/1942/11054
DOI: 10.1242/jcs.066050
ISI #: 000277357400006
ISSN: 0021-9533
Category: A1
Type: Journal Contribution
Validation: ecoom, 2011
Appears in Collections: Research publications

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