Epigenetic Regulation Of Axon Regeneration and Glial Activation in Injury Responses

Frontiers in Genetics, 2019 · DOI: 10.3389/fgene.2019.00640 · Published: July 9, 2019

Regenerative Medicine Neurology Genetics

Simple Explanation

Injury to the nervous system triggers a multicellular response in which epigenetic mechanisms play an important role in regulating cell type-specific transcriptional changes. We specifically discuss regeneration-associated transcriptional modules comprised of transcription factors and epigenetic regulators that control axon growth competence. Better understanding of the cell type-specific epigenetic plasticity might provide new avenues to harness its vast potential to promote long-lasting functional recovery after injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Peripheral axotomy of DRG neurons elicits unique chromatin alterations with corresponding transcriptional responses.
2
Peripheral but not central axotomy results in global enrichment of histone H3 and H4 acetylation (H3ac and H4ac) in DRG neurons.
3
A recent study linked m6A methylation to axon regeneration in conditioned DRG neurons.

Research Summary

Here, we summarize recent progress in characterizing neuronal intrinsic and extrinsic chromatin reconfigurations and epigenetic changes triggered by axonal injury that shape neuroplasticity and glial functions. We also review epigenetic regulation of neuroinflammation and astroglial responses that impact neural repair. These advances provide a framework for developing epigenetic strategies to maximize adaptive alterations while minimizing maladaptive stress responses in order to enhance axon regeneration and achieve functional recovery after injury.

Practical Implications

Epigenetic Strategies for Axon Regeneration

Developing epigenetic strategies to maximize adaptive alterations while minimizing maladaptive stress responses to enhance axon regeneration and achieve functional recovery after injury.

Targeted Chromatin Remodeling

Fine-tuning epigenetic strategies for targeted chromatin remodeling to account for intrinsic cell-type differences in chromatin state and pro-regenerative gene programs.

Combinatorial Epigenetic Strategies

Exploring combinatorial epigenetic strategies to achieve simultaneous enhancement of neuronal intrinsic axon growth potential and modulation of glial inflammatory responses.

Study Limitations

1
Use of whole neural tissue for epigenomic studies doesn’t distinguish cell-type specific epigenetic changes.
2
Roles of new epigenetic mechanisms in CNS injury are poorly understood.
3
Poorly understood dynamics of DNA methylation and hydroxymethylation and their roles in CNS axon regeneration.

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