Sulfation patterns and their effects
One way to alter GAG function is by sulfating patterns, which are patterns of sulfuric acid groups on sugar chains. Shay-wilson's team is interested in how these sulfation patterns change and how they might regulate biological processes such as neuroplasticity and social memory. One day, researchers could also modulate these functions to treat central nervous system injuries, neurodegenerative diseases, or psychiatric disorders.
When the team deleted the Chst11 gene, which is responsible for the formation of the two main sulfated modes of chondroitin sulfate, the mice developed defects in the network around neurons. In the absence of the sulphated pattern, however, the number of neuronal networks actually increased, changing the type of synaptic connections between neurons. In addition, these mice were unable to recognize mice they had previously been exposed to, suggesting that these patterns affect social memory.
Memory and healing potential
Interestingly, these networks may be more dynamic than previously thought - and they may play a role in both childhood and adulthood. When the researchers specifically targeted Chst11 in the brains of adult mice, they found that it had the same effect on perineural cell networks and social memory.
"This result suggests that it may be possible to manipulate these networks during adolescence or adulthood, potentially rewiring or strengthening certain synaptic connections," Shea-Wilson said.
In other recent experiments, the team wanted to understand how GAGs and their sulfation patterns affect axon regeneration, or the ability of neurons to rebuild themselves after injury. The researchers are now working to identify protein receptors that can bind to specific sulfated patterns.
So far, they have found that specific groups cause these receptors to cluster together on the cell surface, inhibiting regeneration. Blocking this process could create tools or treatments that promote axon regeneration. A greater understanding of this process could one day help repair damage caused by certain neurodegenerative diseases or strokes, Hsieh-Wilson said.
