Huang Shu-Bing, Zhao Hou-De, Wang Lin-Fang, Sun Meng-Fei, Zhu Ying-Li, Wu Yi-Bo, Xu Yi-Da, Peng Shi-Xiao, Cui Chun, Shen Yan-Qin
Neuroscience Center, Jiangnan University Medical School, Wuxi, China.
Neuroscience Center, Jiangnan University Medical School, Wuxi, China; Affiliated Hospital of Jiangnan University, Human Reproductive and Genetic Center, Wuxi, China.
Biochem Biophys Res Commun. 2017 Jul 29;489(3):275-280. doi: 10.1016/j.bbrc.2017.05.158. Epub 2017 May 27.
Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI. Immunofluorescence results showed that intradiencephalon HA administration increased the activated microglia 3 days post injury (dpi), promoted the proliferation of radial glial cells at 7 dpi and affected the morphology of radial glial cells at 11 dpi. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that intradiencephalon HA administration also reduced the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor1 (IGF-1) at the lesion site, however, had no effect on the expression of pro-inflammatory factors such as TNF-alpha and IL-1 beta. Hence, our data suggested that exogenous intradiencephalon HA retarded locomotor recovery in spinal cord injured zebrafish via modulating the repair microenvironment.
人类脊髓损伤（SCI）通常会因神经再生能力差而导致损伤部位以下出现不可逆的残疾。相反，斑马鱼在脊髓损伤后表现出显著的再生能力，因此通常作为研究神经再生的动物模型。以往大多数脊髓损伤研究都集中在脊髓损伤的局部部位，很少提及来自脊髓上的信号。在此我们表明，向间脑注射组胺（HA）会抑制成年斑马鱼脊髓损伤后的运动恢复。免疫荧光结果显示，间脑注射HA后，损伤后3天（dpi）激活的小胶质细胞增多，7 dpi时促进了放射状胶质细胞的增殖，并在11 dpi时影响了放射状胶质细胞的形态。此外，定量实时聚合酶链反应（qRT-PCR）结果表明，间脑注射HA还降低了损伤部位包括脑源性神经营养因子（BDNF）和胰岛素样生长因子1（IGF-1）在内的神经营养因子的表达，然而，对促炎因子如TNF-α和IL-1β的表达没有影响。因此，我们的数据表明，外源性间脑HA通过调节修复微环境阻碍了脊髓损伤斑马鱼的运动恢复。
