ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration

The Journal of Neuroscience, 2007 · DOI: 10.1523/JNEUROSCI.5313-06.2007 · Published: July 25, 2007

Regenerative Medicine Neurology Genetics

Simple Explanation

Peripheral nerves can regenerate after injury, unlike central nervous system axons. A prior peripheral nerve injury can 'condition' neurons to grow faster, even enabling central axon regeneration. The study explores how transcription factors like ATF3, induced by peripheral nerve injury, might promote this conditioning effect. The researchers created transgenic mice with constant ATF3 expression in their sensory neurons. They found that these mice exhibited enhanced peripheral nerve regeneration, similar to the effect of a preconditioning injury, indicating ATF3's role in boosting the intrinsic growth state of neurons. However, ATF3 alone couldn't overcome myelin's inhibitory effects or promote central axon regeneration in the spinal cord. This suggests that while ATF3 contributes to nerve regeneration by increasing the neurons' intrinsic growth state, other factors are necessary for full regeneration, particularly in the CNS.

Study Duration

Not specified

Participants

Adult mice

Evidence Level

Not specified

Key Findings

1
ATF3 enhances the rate of peripheral nerve regeneration to an extent comparable to a preconditioning nerve injury.
2
ATF3 increases neurite elongation of DRG neurons when cultured on permissive substrates but does not overcome the inhibitory effects of myelin.
3
Constitutive ATF3 expression in non-injured adult DRG neurons upregulates some growth-associated genes, such as SPRR1A, but not others like GAP-43.

Research Summary

This study investigates the role of ATF3, a transcription factor induced by peripheral nerve injury, in promoting nerve regeneration. The researchers generated transgenic mice that constitutively express ATF3 in DRG neurons to evaluate its effect on intrinsic growth and regeneration. The findings indicate that ATF3 enhances peripheral nerve regeneration and increases neurite outgrowth on permissive substrates. However, ATF3 alone is not sufficient to overcome myelin inhibition or promote central axonal regeneration. The study concludes that ATF3 contributes to nerve regeneration by increasing the intrinsic growth state of injured neurons, but other factors are required for complete regeneration, especially within the CNS.

Practical Implications

Therapeutic Target Identification

ATF3 is a potential therapeutic target for enhancing peripheral nerve regeneration.

Combination Therapies

Combination therapies targeting ATF3 along with other factors may be necessary for promoting regeneration in the CNS.

Understanding Intrinsic Growth State

Further research is needed to fully understand the mechanisms by which ATF3 regulates the intrinsic growth state of neurons.

Study Limitations

1
The study focuses primarily on peripheral nerve regeneration and does not fully address the complexities of CNS regeneration.
2
Constitutive ATF3 expression may not fully mimic the effects of ATF3 induction after nerve injury.
3
The study identifies some, but not all, of the downstream targets of ATF3 in DRG neurons.

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