Glycobiology is one of the fastest growing field in the natural sciences and is widely relevant to many areas of basic research, biomedicine and biotechnology. Glycobiology began with the discovery of sphingolipids, sphingomyelin and sphingosine by Dr. J. L. W. Thudichum in the late 19th century. Sphingomyelin in the brain constitutes the myelin sheath that allows for nerve jump conduction. It is also well known that polysialic acid binds to neural adhesion molecules and regulates neural plasticity during cerebellar development. The most well-studied glycan biosynthesis process takes place in the endoplasmic reticulum and the Golgi complex.

Unlike protein sequences, which are transient gene products, glycan structures are not directly encoded in the genome, and it is currently difficult to predict the exact structure of the glycans produced in a particular cell, even by analysing the expression of all mRNAs in a single cell. Classical models of glycan biosynthesis have assumed that the group of enzymes involved extends glycans to the luminal side of the Golgi endoplasmic reticulum pathway. Interestingly, it has also been shown that O-GlcNAc, which is present in the nucleus and cytoplasm, competes with protein phosphorylation to regulate intracellular signalling, development, and sugar metabolism. The evolutionary diversity of glycans has excellent advantages for understanding brain cell biology, and neurodevelopmental biology in a variety of animal models and human analyses. The paradigm of brain imaging in glycan biology opens up new frontiers for this era.

A remaining challenge is how to perform relevant quantitative and qualitative analyses on glycosylation changes involved in neurodegenerative diseases and psychiatric disorders, and how these relate to the exacerbation of symptoms, in order to treat and prevent them.

There are major frontiers in the development of new brain imaging techniques and theories to visualize multicellular biological regulation derived from the diversity of glycoside structures in the brain, including:

1. Glycosylation control systems for imaging in individual organisms and brain cells.
2. Brain imaging technology of glycomics: Imaging glycans with lectins and antibodies, Imaging glycans with biorthogonal chemical reporters, Metabolic labeling of glycan subtypes with chemical reporters, Imaging mass spectrometry (IMS) and MNR, and Crystal structure of glycoproteins.
3. Application of brain imaging using glycomics to animal models for the analysis of brain function and behavior.

This Research Topic focuses on 3D volume imaging of the brain to study glycosylation in animal models and human samples. More concretely, the aim of this project is not to analyse the structure of glycans expressed in all brain cells, but to identify the glycans that are essential for the formation of specific brain structures and visualize them by brain imaging.

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Frontiers in Neuroanatomy

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