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Cited by 70Proteoglycans and glycosaminoglycans researchNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan

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Miyata, Shinji, Kitagawa, Hiroshi·2016·Neural Plasticity
DOI 10.1155/2016/1305801PMC PMC4738747
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Abstract

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.

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  • Microgliosis represents a potential mechanism driving PNN loss in models of neurodegeneration.

    “Recent work suggests that microgliosis represents a potential mechanism driving PNN loss in models of neurodegeneration (Miyata et al. 2012; Miyata & Kitagawa 2016; Crapser et al. 2021)”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Miyata & Kitagawa 2016

    The Introduction and Results §3.3 describe altered PNNs in mice with increased chondroitin 6-sulfation, while the Discussion addresses aggrecan condensation and glia-dependent PNN formation. Searches for microgliosis, microglial PNN degradation, and neurodegeneration found no passage linking microgliosis to PNN loss in models of neurodegeneration. (LLM, conf=0.77)

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Cited by

Sorted by citations

Authors
Miyata, S., & Kitagawa, H.
Affiliations
  • Bioscience and Biotechnology Center, Nagoya University (JP)
  • Kobe Pharmaceutical University (JP)
Corresponding author
Kitagawa, Hiroshi
ORCID
Venue
Neural Plasticity
Publisher
Wiley
Published
2016
Volume
2016
Pages
1-13
ISSN
  • 1687-5443 (ISSN-L)
  • 2090-5904
DOI
10.1155/2016/1305801
PMC
PMC4738747
OpenAlex
W2233246773
Cited by
70
References
12
Citations by year
2026: 8 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 13 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 4 · 2016: 1
FWCI
4.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Neural Plasticity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Japan Society for the Promotion of Science (16H05088, 25293014, 25860057, 23110003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
perineuronal nets, aggrecan, chondroitin sulfate proteoglycans, extracellular matrix, ADAMTS proteases, brain aging, sulfation patterns
MeSH terms
ADAMTS Proteins, Carbohydrate Sulfotransferases, Animals, Brain, Chondroitin Sulfates, Extracellular Matrix, Neurons, Sulfotransferases, Mice, Aggrecans

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