PUBLICATION
An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish
- Authors
- Huang, C.X., Zhao, Y., Mao, J., Wang, Z., Xu, L., Cheng, J., Guan, N.N., Song, J.
- ID
- ZDB-PUB-211211-9
- Date
- 2021
- Source
- Nature communications 12: 7093 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE182868, GEO:GSE182869, GEO:GSE182911
- MeSH Terms
-
- Spinal Cord/physiopathology
- Spinal Cord Injuries*/genetics
- Spinal Cord Injuries*/metabolism
- Spinal Cord Injuries*/pathology
- Serotonergic Neurons/pathology
- Serotonergic Neurons/physiology*
- Animals
- Electrophysiology
- Recovery of Function*
- Interneurons
- Axons/physiology*
- Serotonin/metabolism
- Zebrafish
- Locomotion
- Receptors, Serotonin/genetics
- Receptors, Serotonin/metabolism
- PubMed
- 34876587 Full text @ Nat. Commun.
Citation
Huang, C.X., Zhao, Y., Mao, J., Wang, Z., Xu, L., Cheng, J., Guan, N.N., Song, J. (2021) An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish. Nature communications. 12:7093.
Abstract
Spinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration. Here, we use a two-cut SCI model to investigate whether recovery of locomotion can occur independently of supraspinal connections. Using this injury model, we show that injury induces the localization of a specialized group of intraspinal serotonergic neurons (ISNs), with distinctive molecular and cellular properties, at the injury site. This subpopulation of ISNs have hyperactive terminal varicosities constantly releasing serotonin activating 5-HT1B receptors, resulting in axonal regrowth of spinal interneurons. Axon regrowth of excitatory interneurons is more pronounced compared to inhibitory interneurons. Knock-out of htr1b prevents axon regrowth of spinal excitatory interneurons, negatively affecting coordination of rostral-caudal body movements and restoration of locomotor function. On the other hand, treatment with 5-HT1B receptor agonizts promotes functional recovery following SCI. In summary, our data show an intraspinal mechanism where a subpopulation of ISNs stimulates axonal regrowth resulting in improved recovery of locomotor functions following SCI in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping