The roles of neuronal and glial precursors in overcoming chondroitin sulfate proteoglycan inhibition

Exp Neurol, 2012 · DOI: 10.1016/j.expneurol.2012.03.017 · Published: June 1, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following spinal cord injury, the glial scar that forms contains molecules called chondroitin sulfate proteoglycans (CSPGs) that inhibit axon regeneration. This study explores how neuronal and glial precursor cells (NRPs and GRPs) can overcome this inhibition. The study found that neurons derived from NRPs can extend axons across CSPG barriers, unlike typical sensory neurons. This ability is linked to lower levels of CSPG receptors (PTPσ and LAR) on the NRP-derived neurons. Additionally, factors secreted by GRPs can modify CSPGs, reducing their inhibitory effects on axon growth. These findings suggest that NRPs and GRPs can be used to promote regeneration after spinal cord injury.

Study Duration

Not specified

Participants

Embryonic day 7 chicken dorsal root ganglia, rat embryonic day 19 dorsal root ganglia, rat embryonic day 13.5 spinal cords

Evidence Level

In vitro study

Key Findings

1
Neurons derived from NRPs are intrinsically less sensitive to CSPGs, enabling them to extend axons across CSPG-rich areas.
2
NRP-derived neurons have significantly lower levels of CSPG receptors PTPσ and LAR compared to primary sensory neurons.
3
Factors secreted by GRPs can modify CSPGs, reducing their inhibitory effect on axon outgrowth from sensory neurons.

Research Summary

This study investigates the roles of neuronal (NRP) and glial (GRP) precursors in overcoming the inhibitory effects of chondroitin sulfate proteoglycans (CSPGs) after spinal cord injury (SCI). The research demonstrates that neurons derived from NRPs exhibit an intrinsic insensitivity to CSPGs, allowing them to extend axons across CSPG-rich regions, which is correlated with lower levels of CSPG receptors PTPσ and LAR. Furthermore, the study reveals that GRPs secrete factors that can modify CSPGs, reducing their inhibitory properties and promoting axon outgrowth of sensory neurons, suggesting a potential therapeutic strategy for SCI.

Practical Implications

Therapeutic Potential

NRPs and GRPs could be used in cell transplantation strategies to promote regeneration and connectivity in spinal cord injuries.

Targeted Therapies

Understanding the mechanisms by which NRPs overcome CSPG inhibition could lead to targeted therapies that enhance axon regeneration.

CSPG Modification

Identifying the factors secreted by GRPs that modify CSPGs could pave the way for developing interventions that alter the inhibitory properties of the glial scar.

Study Limitations

1
The study is limited to in vitro experiments, and further in vivo studies are needed to confirm the findings.
2
The specific factors secreted by GRPs that modify CSPGs were not identified in this study.
3
The long-term effects and functional outcomes of using NRPs and GRPs in spinal cord injury repair were not assessed.

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