EPILEPSY-SPECIFIC FEATURES OF GLYCAN SIGNATURES IN HUMAN BRAIN TISSUE AND SYNAPTOSOMES

Glycoconjugates play vital roles in neurobiological processes, including tissue patterning, neural development, synaptic formation, and neuronal network remodelling. Terminal monosaccharides of glycan structures determine their specific function; the most common of these – sialic acid – has been shown to promote excitability of neuronal circuits and to cause seizures, a common feature of the epileptic brain. However, whether this is caused by a global increase in sialylation across all brain glycoproteins or synapse-specific changes, and whether there are other significant alterations in the glycosylation of neuronal proteins in the epileptic human brain, has never been investigated.
Therefore, this study used surgically resected human brain tissue to investigate the glycobiology of healthy and epileptic human brain. A comprehensive multi-omics study of epileptic human brain bulk tissue and isolated synaptosomes uncovered new molecular signatures. Combined transcriptomic, proteomic and glycomic analysis identified new candidates influencing synaptic protein function, neuronal signalling, and network excitability - processes disturbed in epilepsy. Results uncovered new glycan structures in the epileptic brain and a uniquely distinct synaptosome glycome profile, marked by a linkage-specific sialylation in epilepsy. The density of sialic acid demonstrated a power to modulate neuronal network connectivity and topology in human brain tissue.
This research bridges the gap between neurobiology and glycoscience, opening new avenues for understanding the complexity of the human brain glycome and its link to epilepsy.