Abstract

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a “hot” topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.

Highlights

  • Glycans are diverse and complex structured sugar chains and crucial to many biological processes in all living organisms

  • On-tissue spatially resolved glycoproteomics strategies combined with MALDI-Mass spectrometry imaging (MSI) demonstrated the global dysregulation of N-linked, O-linked glycans in canine glioma biopsies tissue (Malaker et al, 2020)

  • Using MALDI-MSI, several types of gangliosides were spatially visualized in FF mice brain tissue without PNGase F digestion (Figure 3B; Andres et al, 2020)

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Summary

INTRODUCTION

Glycans are diverse and complex structured sugar chains and crucial to many biological processes in all living organisms. Current technological developments in instrumentation and software have made MSI an analytical tool capable of identifying and characterizing a wide range of molecular species while simultaneously imaging their spatial distributions with accurate mass measurements. MSI is an emerging tool that offers label-free imaging of the tissue glycome allowing the detection of several glycans at a time, with the spatial distribution and regional heterogeneity with accurate mass matching. Antigen retrieval breaks chemical crosslinking formed by formalin, allowing for efficient digestion It is crucial for unmasking hidden or latent epitopes in preparation and allows for enzymatic access for releasing glycans from the proteins in the tissue.

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