Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

PLoS ONE, 2012 · DOI: 10.1371/journal.pone.0038101 · Published: June 6, 2012

Regenerative Medicine Neurology Genetics

Simple Explanation

Trauma to the spinal cord and brain can result in irreparable loss of function, partly due to inhibition of axon regeneration. Peripheral nervous system (PNS) neurons have increased regenerative ability compared to central nervous system neurons, even in inhibitory environments. Researchers introduced PNS genes into CNS neurons to see if it would enhance neurite growth on inhibitory substrates like CSPGs, identifying several novel genes (GPX3, EIF2B5, RBMX) that promoted this growth.

Study Duration

Not specified

Participants

Postnatal day 8-10 C57/Bl6j mice

Evidence Level

Not specified

Key Findings

1
Several known growth associated proteins potentiated neurite growth on laminin.
2
Novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX).
3
GPX3 significantly increased growth of transfected and non-transfected hippocampal neurons both on CSPG and on laminin.

Research Summary

The study aimed to identify PNS genes that could enhance the regenerative ability of CNS neurons by promoting neurite growth on inhibitory substrates. A high-content screen of over 1100 PNS genes in cerebellar neurons identified several novel genes (GPX3, EIF2B5, RBMX) that promoted neurite growth on CSPGs. Bioinformatic analysis revealed potential targets for future study, including proteases/protease inhibitors, chloride channels, and ubiquitin ligases.

Practical Implications

Therapeutic targets

Identified genes can be potential therapeutic targets for promoting axon regeneration in CNS injuries.

Combination therapies

Combining identified genes with existing regeneration strategies may improve outcomes.

Drug discovery

Findings may lead to the development of novel drugs that enhance axon regeneration.

Study Limitations

1
The estimated false discovery rate for the overall screen, based on # of primary neurites, was 24%
2
Most of the noise was due to variations in experimental sets from different mice and different days.
3
Higher numbers of controls on each plate would likely reduce FDR

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