Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs

eNeuro, 2017 · DOI: http://dx.doi.org/10.1523/ENEURO.0246-17.2017 · Published: August 11, 2017

Simple Explanation

This research investigates how stress and glucocorticoids (GCs), hormones released during stress, affect the growth and regeneration of sensory nerve fibers in mice. It finds that stress can actually promote the growth of these fibers, contrary to some expectations based on brain studies. The study reveals that sensory neurons in the dorsal root ganglia (DRG) have a surprisingly high number of receptors for GCs, even more than brain areas typically associated with stress responses. This suggests sensory neurons are very sensitive to stress hormones. Researchers found that when sensory neurons from stressed mice are grown in the lab, they exhibit more growth and branching. This effect is linked to the activation of GC receptors and the switching on of specific genes in the sensory neurons.

Study Duration

Not specified

Participants

Adult female C57BL/6 mice or Thy1-GFP-M mice

Evidence Level

Not specified

Key Findings

1
DRG sensory neurons express significantly higher levels of glucocorticoid receptors (GRs) compared to brain regions like the hippocampus.
2
Exposure to stress or glucocorticoids increases neurite growth in adult DRG neurons through GR-dependent gene transcription.
3
Prior exposure to acute systemic stress enhances peripheral nerve regeneration in vivo.

Research Summary

The study demonstrates that stress and GCs enhance the sprouting and regenerative growth of adult sensory axons, both in vitro and in vivo, highlighting their role as modifiers of neuronal plasticity. Unlike the conditioning effects of peripheral nerve injury, stress-induced axon growth does not primarily involve the upregulation of traditional regeneration-associated genes (RAGs). The study identifies several transcription factors (TFs) and RAGs with GC-response elements and demonstrates that some of these genes are regulated by stress via GR-dependent mechanisms, particularly the CCAAT/enhancer binding proteins (Cebp).

Practical Implications

Neuropathic Pain Treatment

The findings prompt reconsideration of using steroids to treat inflammation associated with pain, given the role of stress hormones in sensory neuron plasticity.

Stress Management

Stress management may be a crucial component in recovery from nerve injuries, influencing the extent of axonal regeneration.

Drug Development

The identification of novel GR-dependent RAGs opens new avenues for developing targeted therapies to promote nerve regeneration.

Study Limitations

1
The study primarily focuses on female mice, limiting generalizability to males.
2
The precise mechanisms by which Cebps regulate stress-induced neurite growth require further investigation.
3
The study does not fully explore the effects of GR activation on neural plasticity in various cell types beyond sensory neurons, such as glia and other neurons.

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