A protective action of chondroitin sulfate proteoglycans against neuronal cell death induced by glutamate
Abstract
The role of chondroitin sulfate proteoglycans (CSPGs) on excitotoxic cell death and long-term survival of neurons were investigated in primary cultured neurons of the rat cortex. Soluble CSPGs were prepared from 10-day-old and adult rat brains by the ion-exchange chromatography on DEAE-Sephacel. CSPGs were added to the culture medium on culture day 4, and glutamate neurotoxicity was examined on culture day 7 by both microscopic cell count and measurement of lactate dehydrogenase activity in culture media. The effect on long-term survival was evaluated by counting viable neurons until culture day 28. CSPGs and core proteins, but not glycosaminoglycan chains (GAGs), protected cultured neurons from excitotoxic cell death induced by 24 h exposure to 1 mM glutamate, but CSPGs did not promote the long-term survival of neurons. The neuroprotective effect of CSPGs and core proteins was dose-dependent with ED50 about 10 microM hexuronate and 2 micrograms/ml protein respectively. This effect was not considered to be due to adsorption of glutamate by CSPGs because [3H]glutamate was not adsorbed by CSPGs added to the culture medium. Based on these findings, we suggested that CSPGs may exert their neuroprotective action through molecular interactions with the binding sites on neuronal membrane, neurotrophic factors, or other extracellular matrix molecules and may be involved in the pathogenesis of neuronal cell death in acute pathological conditions and chronic degenerative diseases of the brain.
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GM6001 increased the number of FSNs, most likely due to the known neuroprotective effect of PNNs shielding FSNs from glutamate excitotoxicity.
“In addition, GM6001 increased the number of FSNs most likely due to the known neuroprotective effect of the PNNs33 shielding FSNs from glutamate excitotoxicity33.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [33]
PNNs and CSPGs protect neurons from oxidative stress and glutamate excitotoxicity, and combined actions of glioma-released proteases and Glu might explain the selective vulnerability of PV neurons over principal neurons in the PTC.
“PNNs and CSPGs play crucial roles in protecting neurons from oxidative stress33 and glutamate excitotoxicity42 and combined actions of glioma-released proteases and Glu might explain the selective vulnerability of PV neurons over principle neurons in the PTC.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [33]
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- Authors
- Okamoto, M., Mori, S., & Endo, H.
- Affiliations
- Okayama University (JP)
- Corresponding author
- Okamoto, Motoi
- ORCID
- Mori, Shuji
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1994-02
- Volume
- 637
- Issue
- 1-2
- Pages
- 57-67
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2022728601
- Cited by
- 59
- References
- 66
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2012: 1
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- chondroitin sulfate proteoglycans, neuroprotection, excitotoxicity, glutamate excitotoxicity, neuronal cell death, core protein, glycosaminoglycan chains, cortical neurons, extracellular matrix, neurotrophic factors
- MeSH terms
- Animals, Cells, Cultured, Cellulose, Chondroitin Sulfates, Chromatography, Ion Exchange, Electrophoresis, Polyacrylamide Gel, Glutamates, Glycosaminoglycans, L-Lactate Dehydrogenase, Neurons, Proteoglycans, Electrophoresis, Gel, Two-Dimensional, Cell Death, Rats, Sprague-Dawley, Excitatory Amino Acid Antagonists, Glutamic Acid, Rats
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