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Cited by 121Nerve injury and regenerationProteoglycans and glycosaminoglycans researchSpinal Cord Injury Research

6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

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Lin, Rachel, Rosahl, Thomas W., Whiting, Paul J., Fawcett, James W., Kwok, Jessica C. F.·2011·PLoS ONE
DOI 10.1371/journal.pone.0021499PMC PMC3128591
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Abstract

Chondroitin sulphate proteoglycans (CSPGs) upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs). Chondroitin 6-sulphotransferase-1 (C6ST-1) is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs). Using C6ST-1 knockout mice (KO), we studied post-injury changes in chondroitin sulphotransferase (CSST) expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT) showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury.

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  • 6-O-sulfation is dominant in the juvenile brain to produce C6S, which is more permissive.

    “Specifically, 6--O--sulfation is dominant in the juvenile brain to produce C6S, which is more permissive (Lin et al., 2011;Miyata et al., 2012)”

    From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Lin et al., 2011

    The Introduction says 6-sulphated GAG predominates in embryos and shifts toward 4-sulphated GAG in adults. The Discussion describes 6-sulphated GAG as more permissive to axon regeneration. The cited passages do not establish that 6-O-sulfation is dominant specifically in the juvenile brain; they describe the embryonic developmental stage instead. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Chondroitin 4-sulphates are inhibitory, chondroitin 6-sulphates are more permissive to plasticity and regeneration, and the balance between C6S and C4S regulates neuroplasticity.

    “While chondroitin 4-sulphates (C4S) are inhibitory [5], chondroitin 6-sulphates (C6S) are more permissive to plasticity and regeneration [173, 174], and the balance between C6S and C4S regulates neuroplasticity.”

    From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [174]

    The Discussion (page unavailable) concludes that 6-sulphated chondroitin is permissive for axonal regeneration. It does not establish that C6S is more permissive for plasticity or that the C6S–C4S balance regulates neuroplasticity: the authors found that loss of C6ST-1 did not increase adult CNS plasticity. The separate C4S-inhibition clause is cited to [5], not to this paper. (LLM, conf=0.86)

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Research works printed but not linked: 37

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Cited by

Sorted by citations

Authors
Lin, R., Rosahl, T. W., Whiting, P. J., Fawcett, J. W., & Kwok, J. C. F.
Affiliations
  • University of Cambridge (GB)
  • MSD (UK) Limited (United Kingdom) (GB)
Corresponding author
Kwok, Jessica C. F.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-07-01
Volume
6
Issue
7
Pages
e21499
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0021499
PMC
PMC3128591
OpenAlex
W2062304803
Cited by
121
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 12 · 2012: 7
FWCI
3.98
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Christopher and Dana Reeve Foundation
  • Pfizer
  • Wellcome Trust
  • European Commission
  • Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords
chondroitin sulfate proteoglycans, glial scar, axon regeneration, central nervous system injury, peripheral nerve injury, axonal retraction, extracellular matrix, functional recovery, plasticity
MeSH terms
Carbohydrate Sulfotransferases, Animals, Axons, Behavior, Animal, Neuronal Plasticity, Chondroitin Sulfate Proteoglycans, Regeneration, RNA, Messenger, Spinal Cord, Substantia Nigra, Sulfates, Sulfotransferases, Up-Regulation, Gene Expression Regulation, Enzymologic, Peripheral Nervous System, Hand Strength, Mice, Gene Knockout Techniques

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