The Application of Omics Technologies to Study Axon Regeneration and CNS Repair

F1000Research, 2019 · DOI: 10.12688/f1000research.17084.1 · Published: March 20, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Traumatic brain and spinal cord injuries often lead to permanent disabilities, and currently, there are no effective treatments to fully restore function. However, advancements in omics technologies, bioinformatics, and imaging techniques are uncovering novel cellular and molecular targets that could potentially be manipulated to repair the injured central nervous system. Omics technologies such as epigenomics, transcriptomics, proteomics, and metabolomics are providing unprecedented insight into how injuries to the brain or spinal cord affect genes, molecules, cells and body systems. This insight allows us to see which pathways may be critical regulators of effective axon growth as well as regeneration and remodeling of both injured and spared neural circuits. By studying genetic, proteomic, metabolic, and immunologic functions outside the nervous system using metagenomics, we can learn how microbes in the gut affect the function of neurons and glia in the CNS. Changes in gut microbial communities that occur after brain injury or SCI is a potentially novel target for regulating the structure and function of injured neurons.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Epigenomic screens identified Tet methylcytosine dioxygenase 3 (Tet3) as a critical regulator of axon growth and regeneration. After peripheral nerve lesion (PNL), Tet3 is upregulated along with the epigenetic mark 5-hydroxymethylcytosine (5hmC) in DRG neurons, reversing DNA methylation.
2
Transcriptomics analysis identified Rab27b, a member of the Rab subfamily of GTPases, as a cell-autonomous factor that restricts axon regeneration. Blocking Rab27 in adult neurons may promote axon regeneration by shifting the trafficking of new cell membrane from synapses to the axolemma.
3
Kinomics combined with machine learning identified ribosomal S6 kinase 1 (S6K1) as a negative regulator of axon regeneration. S6K1 inhibition enhances growth of primary mouse hippocampal neurons and promotes regeneration of CST axons into and beyond the lesion site in a model of cervical SCI.

Research Summary

This review highlights recent advances in applying multi-layer omics, new sophisticated bioinformatics tools, and cutting-edge imaging techniques to the study of axon regeneration and rebuilding of injured neural circuitry. These technical advances are revealing an unprecedented number of novel cellular and molecular targets that could be manipulated alone or in combination to repair the injured central nervous system with precision. The review discusses challenges to translate results produced by omics technologies into clinical application to help improve the lives of individuals who have a brain or spinal cord injury. It emphasizes the importance of understanding mechanisms controlling presynaptic biogenesis, synaptic alignment, and connectivity to rebuild injured neural circuits in a functionally meaningful way. The authors conclude that axon regeneration, neuronal metabolism, synapse formation, and functional connectivity need to be spatially and temporally controlled to allow the establishment, refinement, and consolidation of essential neural circuitry. They propose that turning off or reducing intrinsic axon growth ability together with other facilitators may facilitate synapse formation and functional connectivity in the injured CNS.

Practical Implications

Therapeutic Target Identification

Omics technologies can be used to identify new molecular targets for therapeutic interventions to promote axon regeneration and functional recovery after CNS injuries.

Personalized Medicine

Multi-omics data integration, combined with computational methods and artificial intelligence, can enable the selection of personalized treatment strategies for CNS repair.

Drug Repurposing

Existing drugs, such as gabapentinoids, can be repurposed as novel treatments for CNS repair based on their effects on specific molecular targets identified through omics studies.

Study Limitations

1
Prolonged activation of neuron-intrinsic pathways can cause defects in target innervation, negatively impacting functional recovery.
2
Genetic variation exists within model organisms, so treatment strategies need to be validated across different genetic backgrounds.
3
A significant amount of information remains hidden despite the generation of large omics data sets, requiring stringent validation criteria and additional assays.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury