Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 230, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2023.123214
Keywords
Multiple sclerosis; Chondroitin sulfate; Glycosaminoglycans; Experimental autoimmune encephalomyelitis; Extracellular matrix; Hyaluronic acid
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This study investigated the changes in glycosaminoglycans (GAGs) composition and metabolism in the brain during neuroinflammation using a mouse model. The results showed that there were alterations in GAG metabolism during early stages of experimental autoimmune encephalomyelitis (EAE), and these changes may contribute to the progression of inflammatory disorders like multiple sclerosis (MS).
It remains uncertain how brain glycosaminoglycans (GAGs) contribute to the progression of inflammatory dis-orders like multiple sclerosis (MS). We investigated here neuroinflammation-mediated changes in GAG composition and metabolism using the mouse model of experimental autoimmune encephalomyelitis (EAE) and sham-immunized mice as controls. Cerebellum, mid-and forebrain at different EAE phases were investigated using gene expression analysis (microarray and RT-qPCR) as well as HPLC quantification of CS and hyaluronic acid (HA). The cerebellum was the most affected brain region showing a downregulation of Bcan, Cspg5, and an upregulation of Dse, Gusb, Hexb, Dcn and Has2 at peak EAE. Upregulation of genes involved in GAG degradation as well as synthesis of HA and decorin persisted from onset to peak, and diminished at remission, suggesting a severity-related decrease in CS and increments in HA. Relative disaccharide quantification confirmed a 3.6 % reduction of CS-4S at peak and a normalization during remission, while HA increased in both phases by 26.1 % and 17.6 %, respectively. Early inflammatory processes led to altered GAG metabolism in early EAE stages and subsequent partially reversible changes in CS-4S and in HA. Targeting early modifications in CS could potentially mitigate progression of EAE/MS.
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