Cited by 57Proteoglycans and glycosaminoglycans researchProtease and Inhibitor MechanismsNeuroscience and Neuropharmacology Research

Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex

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Mayer, Joanne, Hamel, Michelle G, Gottschall, Paul E·2005·BMC Neuroscience

Abstract

BACKGROUND: Brevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in the central nervous system (CNS) and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs), that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL). RESULTS: In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral) and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation. CONCLUSION: These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML) is elevated during the initial synaptic reinnervation period (7 days after lesion). Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis.

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Authors
Mayer, J., Hamel, M. G., & Gottschall, P. E.
Affiliations
University of South Florida (US)
Corresponding author
Gottschall, Paul E
Venue
BMC Neuroscience
Published
2005-08-25
Volume
6
Issue
1
Pages
52-52
ISSN
1471-2202 (ISSN-L)
OpenAlex
W2120838014
Cited by
57
References
47
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 1 · 2012: 6
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Alzheimer's Association
  • Shriners Hospitals for Children
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 › Neuroscience and Neuropharmacology Research
Keywords
brevican, ADAMTS, proteolytic cleavage, dentate gyrus, entorhinal cortex lesion, excitotoxic lesions, deafferentation, synaptophysin, extracellular matrix proteoglycans, lecticans, chondroitin sulfate, synaptic density, neuroplasticity, synaptogenesis, axonal sprouting
MeSH terms
Animals, Hydrolysis, Male, Mice, Inbred C57BL, Nerve Regeneration, Nerve Tissue Proteins, Neuronal Plasticity, Peptide Hydrolases, Chondroitin Sulfate Proteoglycans, Excitatory Amino Acid Agonists, Entorhinal Cortex, Dentate Gyrus, Disintegrins, Thrombospondins, Amino Acid Motifs, Lectins, C-Type, Metalloproteases, Mice, ADAM Proteins, Brevican

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