| RRC ID |
70674
|
| 著者 |
Huang CX, Zhao Y, Mao J, Wang Z, Xu L, Cheng J, Guan NN, Song J.
|
| タイトル |
An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
12(1)
|
| ページ |
7093
|
| 公開日 |
2021-12-7
|
| DOI |
10.1038/s41467-021-27419-w
|
| PII |
10.1038/s41467-021-27419-w
|
| PMID |
34876587
|
| PMC |
PMC8651775
|
| MeSH |
Animals
Axons / physiology*
Electrophysiology
Interneurons
Locomotion
Receptors, Serotonin / genetics
Receptors, Serotonin / metabolism
Recovery of Function*
Serotonergic Neurons / pathology
Serotonergic Neurons / physiology*
Serotonin / metabolism
Spinal Cord / physiopathology
Spinal Cord Injuries* / genetics
Spinal Cord Injuries* / metabolism
Spinal Cord Injuries* / pathology
Zebrafish
|
| IF |
12.121
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(UAS:nfsB-mCherry)rw0144
Tg(vglut2a:Gal4)
Tg(UAS:GFP)
Tg(glyt2:GFP) |
