Brain inflammation induces alterations in glycosaminoglycan metabolism and subsequent changes in CS-4S and hyaluronic acid

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Item Type:	Article
Title:	Brain inflammation induces alterations in glycosaminoglycan metabolism and subsequent changes in CS-4S and hyaluronic acid
Creators Name:	Silva, R.V., Biskup, K., Zabala-Jouvin, J.K., Batzdorf, C.S., Stellmach, C., Morr, A.S., Sack, I., Ludwig, A., Blanchard, V. and Infante-Duarte, C.
Abstract:	It remains uncertain how brain glycosaminoglycans (GAGs) contribute to the progression of inflammatory disorders 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.
Keywords:	Multiple Sclerosis, Chondroitin Sulfate, Glycosaminoglycans, Experimental Autoimmune Encephalomyelitis, Extracellular Matrix, Hyaluronic Acid, Animals, Mice
Source:	International Journal of Biological Macromolecules
ISSN:	0141-8130
Publisher:	Elsevier
Volume:	230
Page Range:	123214
Date:	March 2023
Official Publication:	https://doi.org/10.1016/j.ijbiomac.2023.123214
PubMed:	View item in PubMed

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