Comparison of sensory neuron growth cone and filopodial responses to structurally diverse aggrecan variants, in vitro

Exp Neurol, 2013 · DOI: 10.1016/j.expneurol.2013.02.012 · Published: September 1, 2013

Simple Explanation

Following spinal cord injury, a glial scar forms, containing CSPGs that inhibit nerve regeneration. This study explores how different forms of aggrecan (a CSPG) affect the growth cones of nerve cells. The researchers tested five different types of aggrecan on nerve cells in vitro, observing how the growth cones and their filopodia (small, finger-like projections) responded. The study found that different aggrecan structures caused different responses in growth cone behavior, suggesting that the specific structure of CSPGs is critical for neuronal behavior after spinal cord injury.

Study Duration

Not specified

Participants

Chick embryonic dorsal root ganglion (DRG; E9–12) neurons

Evidence Level

In vitro study

Key Findings

1
Mutant CHO-745 aggrecan (lacking chondroitin sulfate chains) permitted extensive growth across the PG stripe.
2
COS-7 derived aggrecan inhibited neurite outgrowth following growth cone contact.
3
CHO-K1 derived aggrecan inhibited neurite outgrowth following filopodia contact, and caused an increase in growth cone area and length.

Research Summary

This study investigates the effects of structurally diverse aggrecan variants on sensory neuron growth cones and filopodia in vitro, modeling their first contact with glial scar CSPGs following spinal cord injury. The researchers used a stripe assay and time-lapse video-microscopy to measure growth cone morphology and behavior before and after contact with different aggrecan preparations. The results showed that neuron morphology and behavior are differentially dependent upon aggrecan structure, and that behavioral changes associated with the approaching growth cone may be predictive of inhibition or growth.

Practical Implications

Therapeutic Targets

Identify cellular targets for promoting axonal regeneration after SCI by understanding the steps necessary for successful regeneration.

Drug Development

Develop and test potential therapeutics that modulate growth cone morphology of regenerating neurons.

Understanding CSPG role

Enhance understanding of CSPGs' multipotent role in injured spinal cord, recognizing their potential for both inhibition and direction of neuronal growth.

Study Limitations

1
Use of embryonic DRG neurons instead of adult DRG neurons.
2
Difficulty in confirming equal concentrations of each aggrecan variant adsorbed to the plate.
3
Heterogeneity in purified aggrecan samples and absence of a clear mechanism of action complicates the interpretation.

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