An insight into new glycotherapeutic in glial inflammation: Understanding the role of glycosylation from acute to chronic phase of inflammation

Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodelling from acute to chronic phases. Therefore, understating the glycan changes in these glial cells is paramount. Herein a lectin microarray was undertaken using a cytokine-driven inflammatory MGC model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. Pearsons correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. Control and LPS treatments were observed to be in dense clusters. This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. However, this modification (upregulation of sialic acid expression) was inhibited by the sialyltransferase inhibitor which indeed modulates the mitochondrial functions. The present study is the first functional investigation of glycosylation modulation in a MGC (MGC) model which elucidates the role of the glycome in neuroinflammation and identified potential therapeutic targets for future glycol-therapeutics in neuroinflammation