An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebraﬁsh

Nature Communications, 2021 · DOI: https://doi.org/10.1038/s41467-021-27419-w · Published: December 3, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries disrupt nerve connections and movement control. This study uses zebraﬁsh, which can regenerate spinal cords, to understand how nerve circuits rebuild after injury. The research identifies a specific group of serotonin-releasing neurons that appear at the injury site. These neurons release serotonin, which helps the spinal cord's nerve fibers regrow. Blocking the serotonin release or the receptors that receive it prevents the nerve fibers from regrowing and stops the recovery of movement, showing that this process is vital for healing.

Study Duration

8 weeks

Participants

Zebraﬁsh

Evidence Level

Level 2: Experimental Study

Key Findings

1
Injury induces a specialized group of intraspinal serotonergic neurons (ISNs) at the injury site.
2
This ISN subpopulation has hyperactive terminals releasing serotonin, which activates 5-HT1B receptors and promotes axon regrowth, especially of excitatory interneurons.
3
Knockout of htr1b (the gene for 5-HT1B receptor) prevents axon regrowth and impairs locomotor function, while treatment with 5-HT1B agonists promotes functional recovery.

Research Summary

This study identifies a subpopulation of injury-induced intraspinal serotonergic neurons (ISNs) in zebraﬁsh that promotes axon regrowth and locomotor recovery after spinal cord injury (SCI). These ISNs release serotonin, activating 5-HT1B receptors, which leads to axon regrowth of spinal excitatory interneurons and reestablishment of spinal central pattern generator (CPG) circuits. The findings suggest potential therapeutic strategies for SCI, including cell transplantation of the identified ISN subpopulation and targeting the 5-HT1B receptor.

Practical Implications

Cell Transplantation Therapy

The serotonergic subpopulation may be amenable to cell transplantation therapy.

Target for treatment after SCI

The 5-HT1B receptor is a good candidate target for treatment after SCI.

Drug Development

Development of drugs that selectively target the 5-HT1B receptor to enhance axon regeneration.

Study Limitations

1
The study is conducted on zebraﬁsh, and the findings may not directly translate to mammals.
2
The precise mechanisms by which 5-HT1B receptor activation promotes axon regrowth require further investigation.
3
The long-term effects of 5-HT1B agonist treatment on spinal cord regeneration and locomotor function need to be evaluated.

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