Chondroitin sulfate metabolism in the brain

AbstractNeural extracellular matrix (ECM) is a complex molecular meshwork surrounding neurons and glial cells in the extracellular space. Structural and functional state of ECM in the brain is tightly regulated by various components of neural ECM such as hyaluronic acid, chondroitin sulfate proteoglycans, link proteins, tenascins, various matrix-modifying enzymes such as chondroitin sulfate synthases and carbohydrate sulfotransferase together with matrix-degrading enzymes. Age-dependent accumulation of ECM molecules is implicated in the age-associated decline in synaptic and cognitive functions. Understanding age-associated changes in the expression of genes involved in regulating various components of ECM can provide an insight into the role of ECM in the aging brain. Hence, in this study, we compared the expression levels of ECM regulating genes in three groups of mice: 2-3 months old mice (2-3M), 22- to 26-month-old mice (22-26M) and more than 30-month-old mice (>30M). Using qPCR, we discovered that in the hippocampus of >30M old mice, the majority of ECM related genes are downregulated, while genes related to neuroinflammation are highly upregulated. This pattern was accompanied by a decrease in cognitive performance of the >30M old mice and was most correlated among ECM-related genes with the downregulation of carbohydrate sulfotransferase 3 (CHST3) gene expression. Interestingly, in 24-26M mice, no general decrease in the expression of ECM related genes was observed, although we still found the upregulation in neuroinflammatory genes and downregulation of CHST3. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region of CHST3 gene in non-neuronal (NeuN-negative) but not in neuronal (NeuN-positive) cells. We conclude that in 22-26 M old brains there are minor changes in expression of the studied bona fide neural ECM genes but there is a prominent epigenetic dysregulation of the CHST3 gene responsible for 6-sulfation of chondroitin sulfates, which may lead to impaired brain plasticity and cognitive decline.

Download Full-text

Variants in chondroitin sulfate metabolism genes in thrombotic storm

Thrombosis Research ◽

10.1016/j.thromres.2017.11.016 ◽

2018 ◽

Vol 161 ◽

pp. 43-51 ◽

Cited By ~ 1

Author(s):

Karen Nuytemans ◽

Thomas L. Ortel ◽

Lissette Gomez ◽

Natalia Hofmann ◽

Natalie Alves ◽

...

Keyword(s):

Chondroitin Sulfate ◽

Sulfate Metabolism

Download Full-text

Altered glycosaminoglycan production by HL-60 cells treated with 4- methylumbelliferyl-beta-D-xyloside

Blood ◽

10.1182/blood.v66.4.866.866 ◽

1985 ◽

Vol 66 (4) ◽

pp. 866-872 ◽

Cited By ~ 11

Author(s):

SD Luikart ◽

JL Sackrison ◽

CV Thomas

Keyword(s):

Chondroitin Sulfate ◽

Promyelocytic Leukemia ◽

Leukemia Cells ◽

Sulfate Uptake ◽

Myeloid Development ◽

Sulfate Metabolism ◽

The Media ◽

Primary Granules ◽

And Function

Abstract Glycosaminoglycans, mainly chondroitin 4-sulfate, are located in the primary granules of human myeloid cells. These polyanionic carbohydrates are believed to play an important role in leukocyte maturation and function. To study the effect of altered chondroitin sulfate metabolism on human promyelocytic leukemia cells, we have treated HL-60 cells with 4-methylumbelliferyl-beta-D-xyloside. beta-D- Xylosides initiate the synthesis of free chondroitin sulfate chains. Cytochemical studies of treated cells demonstrated a marked increase in cytoplasmic granules stained with cationic dyes. This was confirmed by radiolabeled precursor incorporation studies that demonstrated a 344% increase in 35S-sulfate uptake into glycosaminoglycans associated with the cells and a 39% increase in incorporation into glycosaminoglycans released into the media. Chromatographic analyses of these glycosaminoglycans from treated cells demonstrated that the newly formed chondroitin sulfate chains were not attached to protein core and were of shorter length, but of greater charge density than chondroitin sulfate produced by control cells. Thus, beta-D-xyloside appears to alter the protein linkage, chain length, and sulfation of chondroitin sulfate produced by HL-60 cells, and these changes are morphologically evident. These biochemically altered cells may provide important information concerning the role of these macromolecules in myeloid development.

Download Full-text

Chondroitin sulfate: A key molecule in the brain matrix

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2012.01.004 ◽

2012 ◽

Vol 44 (4) ◽

pp. 582-586 ◽

Cited By ~ 75

Author(s):

J.C.F. Kwok ◽

P. Warren ◽

J.W. Fawcett

Keyword(s):

Chondroitin Sulfate ◽

The Brain ◽

Chondroitin Sulfate A

Download Full-text

DACS, novel matrix structure composed of chondroitin sulfate proteoglycan in the brain

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.10.040 ◽

2007 ◽

Vol 364 (2) ◽

pp. 410-415 ◽

Cited By ~ 17

Author(s):

Noriko Hayashi ◽

Kouko Tatsumi ◽

Hiroaki Okuda ◽

Masahide Yoshikawa ◽

Shigeaki Ishizaka ◽

...

Keyword(s):

Chondroitin Sulfate ◽

Chondroitin Sulfate Proteoglycan ◽

Matrix Structure ◽

Sulfate Proteoglycan ◽

The Brain

Download Full-text

Development and Structural Variety of the Chondroitin Sulfate Proteoglycans-Contained Extracellular Matrix in the Mouse Brain

Neural Plasticity ◽

10.1155/2015/256389 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 24

Author(s):

Noriko Horii-Hayashi ◽

Takayo Sasagawa ◽

Wataru Matsunaga ◽

Mayumi Nishi

Keyword(s):

Extracellular Matrix ◽

Chondroitin Sulfate ◽

Brain Stem ◽

Cranial Nerves ◽

Lectin Histochemistry ◽

Chondroitin Sulfate Proteoglycans ◽

Amygdaloid Nucleus ◽

Critical Periods ◽

Structural Variety ◽

The Brain

Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In adult mammals, CSPGs form the specialized ECM structure perineuronal nets (PNNs) that surround somata and dendrites of certain types of neurons. PNNs restrict synaptic plasticity and regulate the closure of critical periods. Although previous studies have examined the starting period of PNN formation, focusing on primary sensory cortices, there are no systematic studies at the whole brain level. Here, we examined the starting period of PNN formation in male mice ranging in age from postnatal day 3 to week 11, mainly focusing on several cortical areas, limbic structures, hypothalamus, and brain stem, using lectin histochemistry withWisteria floribundaagglutinin (WFA). Results showed that early PNN formation was observed in several reticular formations of the brain stem related to the cranial nerves and primary somatosensory cortices. In the limbic system, PNN formation in the hippocampus started earlier than that of the amygdala. Furthermore, in the medial amygdaloid nucleus and some hypothalamic regions, WFA labeling did not show typical PNN-like forms. The present study suggests spatiotemporal differences at the beginning of PNN formation and a structural variety of CSPG-contained ECM in the brain.

Download Full-text