6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

Following injury to the central nervous system, axons face challenges in regenerating due to inhibitory molecules in the glial scar, particularly chondroitin sulphate proteoglycans (CSPGs). This study investigates whether increasing 6-sulphated glycosaminoglycans (GAGs) after injury inhibits regeneration or promotes a permissive environment. The researchers used C6ST-1 knockout mice (KO) to study the effects of chondroitin 6-sulphates on axon regeneration in both the central and peripheral nervous systems. They examined regeneration of nigrostriatal axons and repair of the median and ulnar nerves. The results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration. The balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury.

• 1
  C6ST-1 knockout mice showed diminished regeneration of nigrostriatal TH-positive axons compared to wild-type animals after CNS injury.
• 2
  In the PNS, C6ST-1 knockout mice showed similar regenerative ability to wild-type animals after median and ulnar nerve repair.
• 3
  After CNS injury, wild-type animals showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2.