Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry
Open accessAbstract
Chondroitin sulfates (CS) are long, negatively charged, unbranched glycosaminoglycan (GAG) chains attached to CS-proteoglycan (CSPG) core proteins that comprise the glycan component in both loose interstitial extracellular matrices (ECMs) and in rigid, structured perineuronal net (PNN) scaffolds within the brain. As aberrant CS-PNN formations have been linked to a range of pathological states, including Alzheimer's disease (AD) and schizophrenia, the analysis of CS-GAGs in brain tissue at the disaccharide level has great potential to enhance disease diagnosis and prognosis. Two mass-spectrometry (MS)-based approaches were adapted to detect CS disaccharides from minute fixed tissue samples with low picomolar sensitivity and high reproducibility. The first approach employed a straightforward, quantitative direct infusion (DI)-tandem mass spectrometry (MS/MS) technique to determine the percentages of Δ4S- and Δ6S-CS disaccharides within the 4S/6S-CS ratio, while the second used a comprehensive liquid chromatography (LC)-MS/MS technique to determine the relative percentages of Δ0S-, Δ4S-, Δ6S-, Δ4S6S-CS and Δ2S6S-CS disaccharides, with internal validation by full chondroitin lyase activity. The quantitative accuracy of the five primary biologically relevant CS disaccharides was validated using a developmental time course series in fixed rodent brain tissue. We then analyzed the CS disaccharide composition in formalin-fixed human brain tissue, thus providing the first quantitative…
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The authors previously optimized a liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique capable of quantifying the relative abundance of each non-, mono-, and di-sulfated CS isomer extracted from fixed mouse and human brain tissues using ChABC enzymatic digestion.
“We previously optimized a liquid chromatography–tandem mass spectrometry (LC-MS/MS) technique capable of quantifying the relative abundance of each non-, mono-, and di-sulfated CS isomer extracted from fixed mouse and human brain tissues using ChABC enzymatic digestion (Alonge et al. 2019).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Alonge et al. 2019
CS disaccharides were isolated and quantified according to previously published methods.
“CS disaccharides were isolated and quantified according to our previously published methods (Alonge et al. 2019).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Alonge et al. 2019
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Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration
Logsdon, A. F., Foresi, B., Hu, S. J., Quah, E., Meuret, C. J., Le, J. P., Hendrickson, A. S., Redford, I. K., Kumar, A., Phan, B. A., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16067 · Cited by 16 · see citing works
Self-citation
- Authors
- Alonge, K. M., Logsdon, A. F., Murphree, T. A., Banks, W. A., Keene, C. D., Edgar, J. S., Whittington, D., Schwartz, M. W., & Guttman, M.
- Affiliations
- University of Washington (US)
- Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
- ORCID
- Venue
- Glycobiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-16
- Volume
- 29
- Issue
- 12
- Pages
- 847-860
- ISSN
- 0959-6658 (ISSN-L)
- 1460-2423
- PMC
- PMC6861844
- OpenAlex
- W2977439948
- Cited by
- 38
- References
- 8
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Glycobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01GM127579, RO1DK083042, R01AG046619, T32DK00724740, T32AG052354, P50AG005136)
- Nancy and Buster Alvord Endowment
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- chondroitin sulfate, sulfation patterns, glycosaminoglycans, perineuronal nets, extracellular matrix, formalin-fixed tissue, Alzheimer's disease, schizophrenia, human brain tissue, proteoglycans
- MeSH terms
- Animals, Brain Chemistry, Chondroitin Sulfates, Female, Humans, Male, Mice, Inbred C57BL, Spectrometry, Mass, Electrospray Ionization, Mice, Tandem Mass Spectrometry
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