Reshaping the chromatin landscape after spinal cord injury

Front Biol (Beijing), 2014 · DOI: 10.1007/s11515-014-1329-8 · Published: October 1, 2014

Simple Explanation

After a spinal cord injury, the connections between neurons are severed, leading to neurological problems. The body tries to adapt by changing how genes are transcribed in specific cells. Chromatin regulators, which control how DNA is packaged, play a key role in adjusting these gene transcription programs. This review discusses how chromatin regulators affect the behavior of neurons and glial cells after a spinal cord injury, focusing on their role in axon growth and wound healing. Modifying the chromatin state, an epigenetic approach, is a promising way to promote neural repair and axon regeneration. Following SCI, little is known about the levels of expression, subcellular localization, transcriptional targets, or biological functions of the various HDAC isoforms in different cell types. What has been shown, however, is that global acetylation levels in the spinal cord are significantly reduced

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Histone deacetylases (HDACs) compact chromatin and generally exert a repressive transcriptional effect.
2
Peripheral axotomy of DRG neurons triggers a retrograde calcium wave propagated to the nucleus to activate protein kinase C (PKCμ), which in turn induces nuclear export of HDAC5.
3
HDAC3 deletion, on the other hand, releases this epigenomic brake and enhances anti-inflammatory properties of macrophages

Research Summary

After spinal cord injury (SCI), connections between neurons are severed, leading to neurological deficits. Understanding the adaptive responses to injury is crucial for targeted therapy to reestablish these connections. Cell-type specific gene transcription programs govern cellular behaviors after injury, with chromatin regulators playing a central role in shaping the chromatin landscape. Epigenetic modulation represents an emerging therapeutic direction to promote neural repair and axon regeneration after SCI. Future studies are required to tease out the contribution of individual chromatin regulators to the pathophysiological events after SCI in order to optimize treatment paradigms.

Practical Implications

Therapeutic Target Identification

Identifying specific chromatin regulators and their genomic targets in SCI can lead to the development of targeted therapies.

Personalized Medicine

Understanding cell-type-specific epigenetic changes can enable personalized treatment strategies to promote axon regeneration and neural repair.

Drug Development

Develop drugs that modulate epigenetic factors to induce an ensemble of regeneration-associated genes (RAGs), creating a proregenerative chromatin landscape.

Study Limitations

1
Limited specificity of pharmacological agents used to study epigenetic modulation in SCI.
2
Lack of knowledge regarding the expression, localization, targets, and functions of HDAC isoforms in different cell types after SCI.
3
The diverse behaviors of different cell types, often exerting opposing functions, are rarely considered together in a particular experimental paradigm.

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