An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish.
An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish.
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损伤诱导的血清素能神经元亚群有助于斑马鱼脊髓损伤后轴突的再生和功能恢复。
DOI：
10.1038/s41467-021-27419-w
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发表时间：
2021-12-07
影响因子：
16.6
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Huang CX;Zhao Y;Mao J;Wang Z;Xu L;Cheng J;Guan NN;Song J
脊髓损伤（SCI）中断了长投射的下行脊髓神经元，并破坏了控制运动的脊髓中枢模式发生器（CPG）。脊髓损伤后脊髓神经回路的重新布线和运动恢复的内在机制尚不清楚。斑马鱼在脊髓损伤后表现出轴突再生和功能恢复，使其成为研究再生机制的可靠模型。在这里，我们使用一个双切口SCI模型来研究运动的恢复是否可以独立于脊髓上的连接发生。使用这种损伤模型，我们表明，损伤诱导的本地化一组专门的脊髓内神经元（ISNs），具有独特的分子和细胞特性，在损伤部位。ISNs的这个亚群具有过度活跃的末端静脉曲张，不断释放5-羟色胺激活5-HT 1B受体，导致脊髓中间神经元的轴突再生。兴奋性中间神经元的轴突再生比抑制性中间神经元更明显。敲除htr 1b阻止脊髓兴奋性中间神经元的轴突再生，负面影响喙尾体运动的协调和运动功能的恢复。另一方面，用5-HT 1B受体激动剂治疗促进SCI后的功能恢复。总之，我们的数据显示了一种脊髓内机制，其中ISNs的亚群刺激轴突再生，从而改善斑马鱼SCI后运动功能的恢复。脊髓损伤后再生的机制尚不清楚。在这里，作者表明，位于损伤部位的椎管内神经元亚群通过5-HT 1B受体刺激中间神经元的轴突再生，导致斑马鱼SCI后功能恢复。
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. The mechanisms involved in regeneration of the spinal cord after injury are unclear. Here, the authors show that a subpopulation of intraspinal serotonergic neurons localized at the injury site stimulates axonal regrowth of interneurons via 5-HT1B receptor, resulting in recovery of function following SCI in zebrafish.
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通过完全脊髓损伤的小鼠的非侵蚀性AAV介导的对前脊髓神经元的操纵改善后肢运动功能。
影响因子：
16.6
作者：
Brommer B;He M;Zhang Z;Yang Z;Page JC;Su J;Zhang Y;Zhu J;Gouy E;Tang J;Williams P;Dai W;Wang Q;Solinsky R;Chen B;He Z
通讯作者：
He Z
影响因子：
3.5
作者：
Fabbiani G;Rehermann MI;Aldecosea C;Trujillo-Cenóz O;Russo RE
通讯作者：
Russo RE
血清素促进斑马鱼脊髓运动神经元的发育和再生。
影响因子：
8.8
作者：
Barreiro-Iglesias A;Mysiak KS;Scott AL;Reimer MM;Yang Y;Becker CG;Becker T
通讯作者：
Becker T
DOI：
10.1002/wdev.301
发表时间：
2018-01
期刊：
Wiley interdisciplinary reviews. Developmental biology
影响因子：
--
作者：
Deneris E;Gaspar P
通讯作者：
Gaspar P
DOI：
10.1073/pnas.1115377109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eklof-Ljunggren, Emma;Haupt, Sabine;El Manira, Abdeljabbar
通讯作者：
El Manira, Abdeljabbar