Heterogeneity in the regenerative abilities of central nervous system axons within species: why do some neurons regenerate better than others?

Neural Regeneration Research, 2020 · DOI: 10.4103/1673-5374.270298 · Published: December 10, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries result in lasting disabilities because the nerve fibers in the central nervous system don't regrow. However, this inability to regrow isn't the same for all nerve cells; it depends on various factors. One key difference in regenerative capacity lies between the central and peripheral nervous systems. Peripheral nerves can regenerate much more effectively due to a more supportive environment and specific molecular programs initiated within the injured nerve cells. Researchers are now focusing on the specific molecular responses inside nerve cells after an injury to understand why some regenerate better than others. This involves studying gene expression patterns, particularly in non-mammalian models that offer simpler systems for analysis.

Study Duration

Not specified

Participants

Animal models: Caenorhabditis elegans, Petromyzon marinus, Danio rerio, rats, cats

Evidence Level

Review

Key Findings

1
Neurons exhibit varying intrinsic regenerative capabilities, influenced by factors like mTOR activity and the expression of specific proteins such as osteopontin.
2
The expression of certain receptors for guidance molecules, like UNC-5 and Neogenin, can inhibit axon regeneration in lampreys, suggesting that blocking these receptors could promote regeneration.
3
Elevated levels of cAMP can promote axon regeneration by converting repulsive signals into attractive ones, particularly in the Mauthner cells of zebrafish.

Research Summary

This review addresses why some neurons regenerate better than others, focusing on intrinsic regenerative capabilities and responses to environmental factors. The study emphasizes the utility of non-mammalian models like lampreys and zebrafish due to their simpler anatomy and identifiable neurons, which facilitate the study of regeneration mechanisms. Key factors influencing regeneration include the expression of specific guidance molecule receptors, mTOR activity, cAMP levels, and the neuron's ability to reseal after injury, all of which can be potential therapeutic targets.

Practical Implications

Therapeutic Target Identification

Identifies potential therapeutic targets (e.g., Neogenin, cAMP pathways) for promoting axon regeneration after CNS injury.

Model Selection for Research

Highlights the advantages of using non-mammalian models (lampreys, zebrafish) to study axon regeneration due to their simpler nervous systems and identifiable neurons.

Personalized Regenerative Strategies

Suggests that understanding the intrinsic differences between neurons can lead to more targeted and effective regenerative therapies.

Study Limitations

1
Mammalian nervous systems impose methodological limitations, such as the difficulty in distinguishing regenerating from non-regenerating neurons.
2
The precise mechanisms differentiating “good-” and “bad-regenerating” neurons in C. elegans have not yet been fully elucidated.
3
The short distances covered by regenerative axon growth in many invertebrate models can make it difficult to distinguish between developmental mechanisms and true regeneration.

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