<i>N</i>-Acetylglucosamine 6-<i>O</i>-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

Ito, Zenya; Sakamoto, Kazunari; Imagama, Shiro; Matsuyama, Yukihiro; Zhang, Haoqian; Hirano, Ken‐ichi; Ando, Kei; Yamashita, Toshio; Ishiguro, Naoki; Kadomatsu, Kenji

doi:10.1523/jneurosci.2570-09.2010

Cited by 66 publications

(60 citation statements)

References 48 publications

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“…5A). The proteoglycan-mediated inhibition of neurite growth was blocked by K-II and C-ABC, and the effects of K-II and C-ABC were comparable to each other, and also consistent with our previous study (Ito et al, 2010). To our surprise, the combination of K-II and C-ABC showed neither synergistic nor additive effects (Fig.…”

Section: Restoration Of Neurite Outgrowth By K-iisupporting

confidence: 92%

“…The granular staining profile in Figure 1 D represented the main source of KS expression, i.e., microglia ( Fig. 1 E), which is consistent with previous reports (Jones and Tuszynski, 2002;Ito et al, 2010). As disulfated KS was still detected after K-II treatment by disaccharide analysis using HPLC (Fig.…”

Section: In Vitro and In Vivo Degradation Of Ks By K-iisupporting

confidence: 89%

“…We previously determined 300 ng/ml as the appropriate concentration of proteoglycans to coat dishes, which did not affect cell attachment but inhibited neurite outgrowth (Ito et al, 2010). Accordingly, the substratum coated with these proteoglycans strongly inhibited neurite outgrowth (Fig.…”

Section: Restoration Of Neurite Outgrowth By K-iimentioning

confidence: 91%

“…We have recently found that mice deficient in the enzyme N-acetylglucosamine 6-O-sulfotransferase-1 lose reactivity to the anti-KS antibody 5D4 in the brain, and show better axonal growth than wild-type mice after a cortical stab wound (Zhang et al, 2006). We have also found that the mice deficient in this enzyme show better motor function recovery and enhanced axonal regeneration/sprouting after SCI (Ito et al, 2010). However, as these knock-out mice lose N-acetylglucosamine 6-Osulfotransferase-1 in every cell in the body, critical questions remain to be answered, e.g., whether KS specifically works in the spinal cord, and how much impact KS has on functional disturbance.…”

Section: Introductionmentioning

confidence: 98%

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Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

et al. 2011

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Chondroitin sulfate (CS) proteoglycans are strong inhibitors of structural rearrangement after injuries of the adult CNS. In addition to CS chains, keratan sulfate (KS) chains are also covalently attached to some proteoglycans. CS and KS sometimes share the same core protein, but exist as independent sugar chains. However, the biological significance of KS remains elusive. Here, we addressed the question of whether KS is involved in plasticity after spinal cord injury. Keratanase II (K-II) specifically degraded KS, i.e., not CS, in vivo. This enzyme digestion promoted the recovery of motor and sensory function after spinal cord injury in rats. Consistent with this, axonal regeneration/ sprouting was enhanced in K-II-treated rats. K-II and the CS-degrading enzyme chondroitinase ABC exerted comparable effects in vivo and in vitro. However, these two enzymes worked neither additively nor synergistically. These data and further in vitro studies involving artificial proteoglycans (KS/CS-albumin) and heat-denatured or reduced/alkylated proteoglycans suggested that all three components of the proteoglycan moiety, i.e., the core protein, CS chains, and KS chains, were required for the inhibitory activity of proteoglycans. We conclude that KS is essential for, and has an impact comparable to that of CS on, postinjury plasticity. Our study also established that KS and CS are independent requirements for the proteoglycan-mediated inhibition of axonal regeneration/sprouting.

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Section: Restoration Of Neurite Outgrowth By K-iisupporting

confidence: 92%

Section: In Vitro and In Vivo Degradation Of Ks By K-iisupporting

confidence: 89%

Section: Restoration Of Neurite Outgrowth By K-iimentioning

confidence: 91%

Section: Introductionmentioning

confidence: 98%

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Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

et al. 2011

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“…The thinly myelinated axons in the shi-NS/PC group could not conduct signals very well, resulting in an increased MEP latency and a smaller amplitude in the shi-NS/PC group compared with the wt-NS/PC group. Recent studies have established MEP as a sensitive technique for recording conduction in the CNS [14,36,[68][69][70]. Eftekharpour et al [56] demonstrated a significantly shortened latency in the spinal cord-evoked potential in adult shiverer mice after wild-type NS/PCs transplantation, suggesting that conduction differences could be owing to spinal cord myelination, all else being equal.…”

Section: Discussionmentioning

confidence: 99%

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

et al. 2011

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Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/ PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord.

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Diverse roles for glycosaminoglycans in neural patterning

Saied-Santiago

Bülow

2017

Developmental Dynamics

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The nervous system coordinates the functions of most multicellular organisms and their response to the surrounding environment. Its development involves concerted cellular interactions, including migration, axon guidance, and synapse formation. These processes depend on the molecular constituents and structure of the extracellular matrices (ECM). An essential component of ECMs are proteoglycans, i.e., proteins containing unbranched glycan chains known as glycosaminoglycans (GAGs). A defining characteristic of GAGs is their enormous molecular diversity, created by extensive modifications of the glycans during their biosynthesis. GAGs are widely expressed, and their loss can lead to catastrophic neuronal defects. Despite their importance, we are just beginning to understand the function and mechanisms of GAGs in neuronal development. In this review, we discuss recent evidence suggesting GAGs have specific roles in neuronal patterning and synaptogenesis. We examine the function played by the complex modifications present on GAG glycans and their roles in regulating different aspects of neuronal patterning. Moreover, the review considers the function of proteoglycan core proteins in these processes, stressing their likely role as co-receptors of different signaling pathways in a redundant and context-dependent manner. We conclude by discussing challenges and future directions toward a better understanding of these fascinating molecules during neuronal development.

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N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

Cited by 66 publications

References 48 publications

Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

Diverse roles for glycosaminoglycans in neural patterning

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