Barreiro-Iglesias Antón, Mysiak Karolina S, Scott Angela L, Reimer Michell M, Yang Yujie, Becker Catherina G, Becker Thomas
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, UK.
Centre for Neuroregeneration, Edinburgh Medical School, Biomedical Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, UK; Technische Universität Dresden, DFG-Center for Regenerative Therapies Dresden, Cluster of Excellence at the TU Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
Cell Rep. 2015 Nov 3;13(5):924-32. doi: 10.1016/j.celrep.2015.09.050. Epub 2015 Oct 22.
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.
与哺乳动物不同，斑马鱼能够再生脊髓运动神经元。在再生过程中，发育信号会重新发挥作用。在此，我们表明，在发育过程中，弥散的血清素促进pMN祖细胞生成脊髓运动神经元，而中间神经元数量保持不变。药理学操作和受体敲低表明，血清素至少部分通过5-HT1A受体发挥作用。在成体中，血清素主要（90%）由来自大脑的下行轴突供应至脊髓。脊髓损伤后，血清素能轴突在损伤部位尾侧退化，但在损伤部位头侧会出芽。毒素介导的损伤部位头侧血清素能轴突消融仅损害该部位运动神经元的再生。相反，腹腔注射血清素使损伤部位尾侧新运动神经元和增殖的pMN样祖细胞数量增加了一倍。这些操作并未改变脊髓内源性血清素能中间神经元的再生。因此，血清素选择性地促进斑马鱼运动神经元的发育和成体再生。
