The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Association between protease-specific proteolytic cleavage of brevican and synaptic loss in the dentate gyrus of kainate-treated rats
Abstract
Proteolytic fragments generated by ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs)-mediated cleavage of the aggregating chondroitin sulfate proteoglycan, brevican, have been identified, but not localized in the CNS. The purpose of this study, using kainate-induced CNS lesion, was to examine the spatial and quantitative relationship between ADAMTS1 and 4 mRNA expression and ADAMTS-mediated cleavage of brevican (as determined by the abundance of the neo-epitope QEAVESE at the C-terminal of the cleaved brevican G1 domain). In untreated rats, in situ hybridization and reverse transcriptase polymerase chain reaction indicated that ADAMTS4 expression was higher than ADAMTS1 and was localized to hippocampus, temporal lobe and other areas of cortex, striatum and hypothalamus. ADAMTS4 mRNA expression in these regions correlated with the presence of the QEAVESE neo-epitope, which was concentrated in perineuronal nets and in neuropil. In rats that seized after kainate, there was a dramatic elevation in ADAMTS1 and ADAMTS4 transcript that correlated and co-localized with a robust elevation in an extractable, 55-kDa fragment of brevican in temporal lobe and hippocampus. This fragment consisted, at least in part, of the ADAMTS-cleaved epitope G1-QEAVESE. The kainate-induced elevation in this ADAMTS-cleaved fragment was localized to amygdaloid and thalamic nuclei, hippocampus, caudate-putamen, cingulate cortex, and the outer molecular layer of the dentate gyrus where it was accompanied by a robust elevation in ADAMTS1 and 4 mRNA and a 28% decline in synaptic density 5 days after kainate.Thus, complexes of extracellular matrix proteins that exist in perineuronal nets and in the neuropil are cleaved by specific matrix-degrading proteases at early time points during excitotoxic neurodegeneration. The observed ADAMTS-induced cleavage of brevican in the dentate outer molecular layer is closely associated with diminished synaptic density, and may, therefore, contribute to synaptic loss and/or reorganization in this region.
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“Moreover, ADAMTS-mediated brevican degradation colocalized with areas of synaptic loss in a kainic acid model of acute neuronal toxicity (Yuan et al., 2002).”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Yuan et al., 2002
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Cites
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Research works printed but not linked: 1
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The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Fawcett, J. W., Oohashi, T., & Pizzorusso, T. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0196-3 · Cited by 589
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Extracellular matrix of the central nervous system: from neglect to challenge
Zimmermann, D. R., & Dours-Zimmermann, M. T. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0485-9 · Cited by 465
The perineuronal net and the control of CNS plasticity
Wang, D., & Fawcett, J. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1375-y · Cited by 373
Brain Extracellular Matrix in Neurodegeneration
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Metadata
- Authors
- Yuan, W., Matthews, R. T., Sandy, J. D., & Gottschall, P. E.
- Affiliations
- University of South Florida (US)
- Yale University (US)
- Corresponding author
- Gottschall, P.E
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 114
- Issue
- 4
- Pages
- 1091-1101
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2048724646
- Cited by
- 109
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 8 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 12
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ag012160-05)
- National Institute on Aging (AG 12160)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- brevican, ADAMTS1, ADAMTS-4, proteolytic cleavage, synaptic loss, dentate gyrus, kainate-induced seizures, excitotoxic neurodegeneration, perineuronal nets, extracellular matrix proteolysis, chondroitin sulfate proteoglycans, synaptic density, hippocampus, amygdala, thalamus
- MeSH terms
- ADAMTS1 Protein, ADAMTS4 Protein, Animals, Antibodies, Denervation, Kainic Acid, Male, Metalloendopeptidases, Nerve Tissue Proteins, Neurotoxins, Peptide Fragments, Procollagen N-Endopeptidase, Chondroitin Sulfate Proteoglycans, RNA, Messenger, Substrate Specificity, Synapses, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Dentate Gyrus, Disintegrins, Lectins, C-Type, Rats, ADAM Proteins, Brevican
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