Chondroitin Sulfate Proteoglycan Immunoreactivity Increases Following Spinal Cord Injury and Transplantation

Lemons, Michele L.; Howland, Dena R.; Anderson, Douglas K.

doi:10.1006/exnr.1999.7184

Cited by 216 publications

(145 citation statements)

References 75 publications

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“…Furthermore, CSPGs produced by neurons and astrocytes form lattice-like perineuronal nets that shroud adult neuronal cell bodies and proximal dendrites [60,61]. Concentrations of some CSPGs increase in humans and animals not only at the SCI site [62][63][64][65][66][67][68][69][70][71] but also rostral [70] and caudal [72] to it.…”

Section: Pharmacological and Gene-delivery Approachesmentioning

confidence: 99%

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

2011

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Summary: Motor, sensory, and autonomic functions can spontaneously return or recover to varying extents in both humans and animals, regardless of the traumatic spinal cord injury (SCI) level and whether it was complete or incomplete. In parallel, adverse and painful functions can appear. The underlying mechanisms for all of these diverse functional changes are summarized under the term plasticity. Our review will describe what is known regarding this phenomenon after traumatic SCI and focus on its relevance to motor and sensory recovery. Although it is still somewhat speculative, plasticity can be found throughout the neuraxis and includes various changes ranging from alterations in the properties of spared neuronal circuitries, intact or lesioned axon collateral sprouting, and synaptic rearrangements. Furthermore, we will discuss a selection of potential approaches for facilitating plasticity as possible SCI treatments. Because a mechanism underlying spontaneous plasticity and recovery might be motor activity and the related neuronal activity, activity-based therapies are being used and investigated both clinically and experimentally. Additional pharmacological and gene-delivery approaches, based on plasticity being dependent on the delicate balance between growth inhibition and promotion as well as the basic intrinsic growth ability of the neurons themselves, have been found to be effective alone and in combination with activitybased therapies. The positive results have to be tempered with the reality that not all plasticity is beneficial. Therefore, a tremendous number of questions still need to be addressed. Ultimately, answers to these questions will enhance plasticity's potential for improving the quality of life for persons with SCI.

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Section: Pharmacological and Gene-delivery Approachesmentioning

confidence: 99%

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

2011

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“…The highly regulated expression of GalNAc-4-ST1 (3,30) in other tissues such as the brain suggests that it will have additional roles that remain to be defined. In addition to their importance for the formation and maintenance of cartilage (31,32), there is also evidence that chondroitin sulfate proteoglycans are important for neural cell adhesion, neurite outgrowth, synaptic plasticity, and regeneration (33)(34)(35)(36)(37). A number of chondroitin sulfate-bearing proteoglycans are produced by tissues (31,32).…”

Section: Chrondroitin-4-sulfotransferase-3mentioning

confidence: 99%

Molecular Cloning and Characterization of Chondroitin-4-O-sulfotransferase-3

Kang

Evers

Xia

et al. 2002

Journal of Biological Chemistry

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We have identified and characterized an N-acetylgalactosamine-4-O-sulfotransferase designated chondroitin-4-sulfotransferase-3 (C4ST-3) (GenBank TM accession number AY120869) based on its homology to HNK-1 sulfotransferase (HNK-1 ST). The cDNA predicts an open reading frame encoding a type II membrane protein of 341 amino acids with a 12-amino acid cytoplasmic domain and a 311-amino acid luminal domain containing a single potential N-linked glycosylation site. C4ST-3 has the greatest amino acid sequence identity when aligned with chondroitin-4-O-sulfotransferase 1 (C4ST-1) (45%) but also shows significant amino acid identity with chondroitin-4-O-sulfotransferase 2 (C4ST-2) (27%), dermatan-4-O-sulfotransferase 1 (29%), HNK-1 ST (26%), N-acetylgalactosamine-4-O-sulfotransferase 1 (26%), and N-acetylgalactosamine-4-Osulfotransferase 2 (23%). C4ST-3 transfers sulfate to the C-4 hydroxyl of ␤1,4-linked GalNAc that is substituted with a ␤-linked glucuronic acid at the C-3 hydroxyl. The open reading frame of C4ST-3 is encoded by three exons located on human chromosome 3q21.3. Northern blot analysis reveals a single 2.1-kilobase transcript. C4ST-3 message is expressed in adult liver and at lower levels in adult kidney, lymph nodes, and fetal liver. Although C4ST-3 and C4ST-1 have similar specificities, the highly restricted pattern of expression seen for C4ST-3 suggests that it has a different role than C4ST-1.We and others have recently reported the cloning and functional characterization of members of the HNK-1 family of sulfotransferases. These include human HNK-1 sulfotransferase (HNK-1 ST) 1 itself (1, 2), GalNAc-4-ST1 (3-5), GalNAc-4-ST2 (5, 6), dermatan-4-sulfotransferase-1 (D4ST-1) (7), chondroitin-4-sulfotransferase-1 (C4ST-1) (8, 9), and chondroitin-4-sulfotransferase-2 (C4ST-2) (8). With the exception of HNK-1 ST itself, which transfers sulfate to the C-3 hydroxyl of terminal glucuronic acid in the sequence GlcUA␤1,3Gal␤1,4GlcNAc-R to produce the HNK-1 epitope SO 4 -3-GlcUA␤1,3Gal␤1,4GlcNAc-R, the members of this family of sulfotransferases are all GalNAc-4-sulfotransferases. GalNAc-4-ST1 and GalNAc-4-ST2 both transfer sulfate to the C-4 hydroxyl of terminal ␤1,4-linked GalNAc on N-linked oligosaccharides such as those found on the glycoprotein hormones lutropin and thyrotropin (10, 11). Whereas C4ST-1, C4ST-2, and D4ST-1 are also GalNAc-4-O-sulfotransferases, they only transfer sulfate to the C-4 hydroxyl of internal ␤1,4-linked GalNAc moieties within the repeating disaccharide sequences found in chondroitin and dermatan (7-9). We now report the cloning of another member of this family of sulfotransferases. Like C4ST-1, this new sulfotransferase, chondroitin-4-sulfotransferase-3 (C4ST-3) transfers sulfate to the C-4 hydroxyl of ␤1,4-linked GalNAc that is flanked by GlcUA residues in chondroitin. In contrast to C4ST-1, C4ST-3 is labile at 37°C and has a restricted distribution, suggesting that it may have a unique biological role in vivo. EXPERIMENTAL PROCEDURES Molecular Cloning of a cDNA Encoding Human Chon...

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“…This glial scar is predominantly formed from extracellular matrix (ECM) molecules expressed by reactive astrocytes although macrophages, microglia, oligodendrocytes, invading Schwann cells and meningeal fibroblasts all contribute to production of the scar matrix (Fawcett and Asher, 1999). Chief of the many ECM molecules that serve to inhibit axonal regeneration are the chondroitin sulfate proteoglycans (CSPGs) (Eddleston and Mucke, 1993;Silver and Miller, 2004) that experience a great increase in expression following SCI (Lemons et al, 1999;McKeon et al, 1991). Both in vitro and in vivo studies have shown that axons do not extend into CSPG-rich ECM (Davies et al, 1997(Davies et al, , 1999McKeon et al, 1991;Meiners et al, 1995;Zuo et al, 1998), and specific CSPGs that inhibit neurite outgrowth have been identified including: aggrecan (Condic et al, 1999), neurocan , phosphocan , brevican (Yamada et al, 1997), versican (Schmalfeldt et al, 2000), and NG2 (Dou and Levine, 1994).…”

Section: Introductionmentioning

confidence: 99%

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

McKillop

Dragan

Schedl

et al. 2012

Glia

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Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic level 9. One week after injury, Sox9 conditional knock-out mice expressed reduced levels of CSPG biosynthetic enzymes (Xt-1 and C4st), CSPG core proteins (brevican, neurocan, and aggrecan), collagens 2a1 and 4a1, and Gfap, a marker of astrocyte activation, in the injured spinal cord compared with controls. These changes in gene expression were accompanied by improved hind limb function and locomotor recovery as evaluated by the Basso Mouse Scale (BMS) and rodent activity boxes. Histological assessments confirmed reduced CSPG deposition and collagenous scarring at the lesion of Sox9 conditional knock-out mice, and demonstrated increased neurofilament-positive fibers in the lesion penumbra and increased serotonin immunoreactivity caudal to the site of injury. These results suggest that SOX9 inhibition is a potential strategy for the treatment of SCI.

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Chondroitin Sulfate Proteoglycan Immunoreactivity Increases Following Spinal Cord Injury and Transplantation

Cited by 216 publications

References 75 publications

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

Molecular Cloning and Characterization of Chondroitin-4-O-sulfotransferase-3

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

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