title: Germline ablation of dermatan-4O-sulfotransferase1 reduces regeneration after mouse spinal cord injury.
abstract: Chondroitin/dermatan sulfate proteoglycans (CSPGs/DSPGs) are major components of the extracellular matrix. Their expression is generally upregulated after injuries to the adult mammalian central nervous system, which is known for its low ability to restore function after injury. Several studies support the view that CSPGs inhibit regeneration after injury, whereas the functions of DSPGs in injury paradigms are less certain. To characterize the functions of DSPGs in the presence of CSPGs, we studied young adult dermatan-4O-sulfotransferase1-deficient (Chst14(-/-)) mice, which express chondroitin sulfates (CSs), but not dermatan sulfates (DSs), to characterize the functional outcome after severe compression injury of the spinal cord. In comparison to their wild-type (Chst14(+/+)) littermates, regeneration was reduced in Chst14(-/-) mice. No differences between genotypes were seen in the size of spinal cords, numbers of microglia and astrocytes neither in intact nor injured spinal cords after injury. Monoaminergic innervation and re-innervation of the spinal cord caudal to the lesion site as well as expression levels of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were similar in both genotypes, independent of whether they were injured and examined 6weeks after injury or not injured. These results suggest that, in contrast to CSPGs, DSPGs, being the products of Chst14 enzymatic activity, promote regeneration after injury of the adult mouse central nervous system.
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rost
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Akyüz
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany; Institute of Histology and Embryology, School of Medicine, University of Belgrade, Višegradska 26, Belgrade, Serbia.
authors.forename: T
authors.initials: T
authors.lastname: Martinovic
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Huckhagel
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany; Experimental Neurophysiology, University Hospital Cologne, Joseph-Stelzmann-Str. 9, D-50931 Köln, Germany; German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, D-53175 Bonn, Germany. Electronic address: igor.jakovcevski@dzne.de.
authors.forename: I
authors.initials: I
authors.lastname: Jakovcevski
authors.affiliation: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany; Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong 515041, PR China; Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA. Electronic address: schachner@stu.edu.cn.
authors.forename: M
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002809:Chondroitin Sulfates / Q000502:physiology*; D003871:Dermatan Sulfate / Q000502:physiology*; D004195:Disease Models, Animal; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D015238:Sulfotransferases / Q000172:deficiency* / Q000235:genetics
chemical_list: D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates; D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1
keywords: HNK-1 family sulfotransferases; chondroitin sulfate; dermatan sulfate; dermatan-4O-sulfotransferase1; regeneration; spinal cord