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Glycosaminoglycans

Glycosaminoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...

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Related Experiment Video

Updated: Jul 27, 2025

3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation

3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation

Published on: October 7, 2015

Chondroitin 4-

Huiqian Huang^1,2, Amélie M Joffrin¹, Yuan Zhao³

¹Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.

Proceedings of the National Academy of Sciences of the United States of America

|June 6, 2023

Summary

This summary is machine-generated.

Altered brain chondroitin sulfate (CS) 4-O-sulfation impacts perineuronal nets, affecting anxiety and social memory. Targeting CS 4-O-sulfation may help treat related cognitive disorders.

Keywords:

chondroitin sulfate (CS)glycans glycosaminoglycans (GAGs)perineuronal nets (PNNs)social memory

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Area of Science:

Neuroscience
Glycobiology
Molecular Biology

Background:

Glycan alterations are linked to aging and neurodegenerative diseases.
Specific glycan roles in emotion and cognition are largely unknown.
Chondroitin sulfate (CS) is a key component of the extracellular matrix in the brain.

Purpose of the Study:

To investigate the role of 4-O-sulfated CS in regulating perineuronal nets (PNNs) and synapse development.
To determine the impact of CS 4-O-sulfation on anxiety and social memory in mice.
To explore therapeutic potential of targeting CS 4-O-sulfation for neuropsychiatric disorders.

Main Methods:

Utilized a combination of chemistry and neurobiology techniques.
Generated mice with brain-specific deletion of CS 4-O-sulfation.
Performed selective ablation of CS 4-O-sulfation in the adult CA2 region.
Employed enzymatic pruning and chemical manipulation of CS 4-O-sulfation levels.

Main Results:

Deletion of CS 4-O-sulfation increased PNN densities in the hippocampus (CA2 region).
This led to imbalanced synaptic ratios, reduced CREB activation, elevated anxiety, and social memory deficits.
Enzymatic PNN pruning reduced anxiety and restored social memory.
Chemical modulation of CS 4-O-sulfation reversibly altered PNN densities and synaptic balance.

Conclusions:

CS 4-O-sulfation is a critical regulator of PNNs and synapse development in the adult brain.
It plays a key role in adult brain plasticity, social memory, and anxiety regulation.
Targeting CS 4-O-sulfation may offer a novel therapeutic strategy for social cognitive dysfunction in neuropsychiatric and neurodegenerative diseases.