Serotonin Promotes Development and Regeneration of Spinal Motor Neurons in Zebrafish.

Serotonin Promotes Development and Regeneration of Spinal Motor Neurons in Zebrafish.
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血清素促进斑马鱼脊髓运动神经元的发育和再生。

DOI:
10.1016/j.celrep.2015.09.050
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发表时间:
2015-11-03
期刊:
影响因子:
8.8
通讯作者:
Becker T
Becker T
中科院分区:
生物学1区
文献类型:
--
作者:
Barreiro-Iglesias A;Mysiak KS;Scott AL;Reimer MM;Yang Y;Becker CG;Becker T

文献摘要

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与哺乳动物不同,斑马鱼可以再生脊髓运动神经元。在再生过程中,发育信号被重新部署。在这里,我们表明,在发展过程中,弥漫性5-羟色胺促进脊髓运动神经元的产生从pMN祖细胞,离开interneuron数不变。药理学操作和受体敲低表明,5-羟色胺至少部分地通过5-HT 1A受体起作用。在成年人中,血清素主要(90%)通过来自大脑的下行轴突供应给脊髓。脊髓损伤后,轴突退化的尾部到病变,但芽头到它。毒素介导的消融的轴突损伤的运动神经元的再生受损的喙也只有在那里。相反,腹膜内注射5-羟色胺使新的运动神经元和病变尾侧增殖的pMN样祖细胞的数量加倍。脊髓内源性多巴胺能中间神经元的再生没有改变这些操作。因此,5-羟色胺选择性地促进斑马鱼运动神经元的发育和成体再生。5-羟色胺是促进成年斑马鱼运动神经元再生的远程信号5-羟色胺作用于pMN样祖细胞的增殖5-羟色胺不影响脊髓神经元的再生外源性5-羟色胺可以补偿内源性5-羟色胺能轴突的损失成年斑马鱼,与哺乳动物相反,再生脊髓神经元。Barreiro-Iglesias等人确定来自下行轴突的5-羟色胺促进受损脊髓中运动神经元的再生,但不影响脊髓神经元再生。5-羟色胺特异性作用于运动神经元的成体祖细胞。
In contrast to mammals, zebrafish regenerate spinal motor neurons. During regeneration, developmental signals are re-deployed. Here, we show that, during development, diffuse serotonin promotes spinal motor neuron generation from pMN progenitor cells, leaving interneuron numbers unchanged. Pharmacological manipulations and receptor knockdown indicate that serotonin acts at least in part via 5-HT1A receptors. In adults, serotonin is supplied to the spinal cord mainly (90%) by descending axons from the brain. After a spinal lesion, serotonergic axons degenerate caudal to the lesion but sprout rostral to it. Toxin-mediated ablation of serotonergic axons also rostral to the lesion impaired regeneration of motor neurons only there. Conversely, intraperitoneal serotonin injections doubled numbers of new motor neurons and proliferating pMN-like progenitors caudal to the lesion. Regeneration of spinal-intrinsic serotonergic interneurons was unaltered by these manipulations. Hence, serotonin selectively promotes the development and adult regeneration of motor neurons in zebrafish. Serotonin is a remote signal promoting motor neuron regeneration in adult zebrafish Serotonin acts on proliferation of pMN-like progenitors Serotonin does not affect regeneration of spinal serotonergic neurons Exogenous serotonin can compensate for the loss of endogenous serotonergic axons Adult zebrafish, in contrast to mammals, regenerate spinal neurons. Barreiro-Iglesias et al. establish that serotonin from descending axons promotes the regeneration of motor neurons in the lesioned spinal cord but leaves spinal serotonergic neuron regeneration unaffected. Serotonin acts specifically on adult progenitor cells for motor neurons.