engleski

Spatio-temporal profiling of the human brain N- glycome

N-glycosylation plays a role in many aspects of nervous system biology including membrane excitability, synaptic transmission, maintenance and differentiation of neural stem cells, neurite outgrowth and neuronal plasticity [1–6]. Yet there are remarkably few studies that have attempted to characterize the N-glycome of the brain in detail [7-10]. An in-depth structural characterization of the neuroglycome is therefore of great importance to gain a better understanding of glycan functions in the central nervous system. The goal of the project was to characterise the spatiotemporal profile of N-glycan structures in the human brain and how they change throughout ontogeny. To achieve this, a new method was developed to allow rapid analysis of N-glycans from brain tissue by HILIC-UPLC. Structural annotation of N-glycans was performed by MALDI-TOF/TOF MS/MS. The main finding from this work is that evolutionarily older brain regions, such as the cerebellum and striatum, tend to contain simpler N-glycans, including a large proportion of oligomannose structures, while more recently evolved brain regions, such as the hippocampus and frontal cortex, tend to have more complex N-glycans, including highly branched, tri- and tetra-antennary structures. Similarly, a shift in the brain N-glycome profile is observed during development with simpler N-glycans, particularly oligomannose structures, being common in the fetal brain, but more complex structures being prevalent in the adult brain. These findings lead us to hypothesize that there is an association between the complexity of N-glycan structures in a given brain region and the level of functional complexity.

Neuroglycobiology ; N-glycome ; N-glycans

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