Germline ablation of dermatan-4O-sulfotransferase1 reduces regeneration after mouse spinal cord injury. (15th January 2016)

• Record Type: Journal Article
• Authors: Rost, S.; Akyüz, N.; Martinovic, T.; Huckhagel, T.; Jakovcevski, I.; Schachner, M.
• Is Part Of: Neuroscience. Volume 312(2016)
• Page Start: 74
• Page End: 85
• Publication Date: 2016-01-15
• Subjects: ChABC chondroitinase ABC -- ChAC chondroitinase AC -- ChAT choline acetyltransferase -- ChB chondroitinase B -- Chst14 carbohydrate sulfotransferase 14 also known as dermatan-4O-sulfotransferase1 -- CS chondroitin sulfate -- CSPG chondroitin sulfate proteoglycan -- DS dermatan sulfate -- DSPG dermatan sulfate proteoglycan -- GFAP glial fibrillary acidic protein -- NG2 new glue 2 also known as chondroitin sulfate proteoglycan 4 (CSPG4) -- MBP myelin basic protein -- SCI spinal cord injury -- TH tyrosine hydroxylase; chondroitin sulfate -- dermatan sulfate -- dermatan-4O-sulfotransferase1 -- HNK-1 family sulfotransferases -- regeneration -- spinal cord; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.11.013
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: We developed mice deficient in Chst14, pivotal enzyme by generation of dermatan sulfate. We performed spinal cord injury in Chst14-deficient mice ( Chst14 −/− ). We observed reduced locomotor recovery after spinal cord injury in Chst14 −/− versus Chst14 +/+ mice. Chst14 ablation slightly reduced axonal regeneration, and had no effect on glial scar formation. 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 6 weeks 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.