Glia maturation factor beta is required for reactive gliosis after traumatic brain injury in zebrafish

Glia maturation factor beta is required for reactive gliosis after traumatic brain injury in zebrafish
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斑马鱼脑外伤后反应性神经胶质增生需要神经胶质成熟因子β

DOI:
10.1016/j.expneurol.2018.04.008
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发表时间:
2018-07
影响因子:
5.3
通讯作者:
Wu Bingyi
Wu Bingyi
中科院分区:
医学2区
文献类型:
--
作者:
Yin Guo;Du Mingjun;Li Rong;Li Ke;Huang Xiaomin;Duan Dongbei;Ai Xiaolan;Yao Fang;Zhang Lanlan;Hu Ziyou;Wu Bingyi

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神经胶质增生是大多数形式的中枢神经系统(CNS)损伤,包括创伤性脑损伤(TBI)后发生的神经病理学的标志。识别控制神经胶质细胞增生的基因可能为不同中枢神经系统损伤的患者提供新的治疗靶点。胶质细胞成熟因子β(GMFB)在大脑发育和应激反应中起关键作用。本研究发现GMFB在成年斑马鱼的端脑中广泛表达。Agmfb突变体斑马鱼是使用CRISPR/Cas9创建的。在未受损伤的斑马鱼端脑中,突变体的胶质纤维酸性蛋白(GFAP)纤维比野生型斑马鱼的纤维排列紊乱,长度较短。在脑损伤后,gmfb突变体显著抑制了静止的I型放射状胶质细胞(RGC)向增殖的II型RGC的转化。突变型胶质细胞损伤后RGC增殖和肥大减少,表明反应性胶质细胞增生性减弱。在gmfb突变体中,也发现脑损伤引起的急性炎症也得到了缓解。形态改变也提示小胶质细胞反应性胶质细胞增生症减弱。在脑外伤的小鼠模型中,GMFB在损伤部位周围的表达增加。GMFB+细胞鉴定为星形胶质细胞和小胶质细胞。综上所述,这些数据表明,GMFB不仅是斑马鱼端脑GFAP纤维正常发育所必需的,而且还促进了脑损伤后反应性胶质细胞的形成。我们的发现提供了新的信息,有助于更好地了解脑外伤后的反应性胶质细胞增生过程。
Gliosis is a hallmark of neural pathology that occurs after most forms of central nervous system (CNS) injuries including traumatic brain injury (TBI). Identification of genes that control gliosis may provide novel treatment targets for patients with diverse CNS injuries. Glia maturation factor beta (GMFB) is crucial in brain development and stress response. In the present study, GMFB was found to be widely expressed in adult zebrafish telencephalon. Agmfbmutant zebrafish was created using CRISPR/cas9. In the uninjured zebrafish telencephalon, glial fibrillary acidic protein (GFAP) fibers ingmfbmutants were disorganized and shorter than wild type zebrafish. After TBI, transformation of quiescent type I radial glial cells (RGC) to proliferative type II RGCs was significantly suppressed in thegmfbmutant. RGC proliferation and hypertrophy post-TBI was reduced ingmfbmutants, indicating that reactive gliosis was attenuated. TBI-induced acute inflammation was also found to be alleviated in thegmfbmutant. Morphological changes also suggest attenuation of microglial reactive gliosis. In a mouse model of TBI, GMFB expression was increased around the injury site. These GMFB+ cells were identified as astrocytes and microglia. Taken together, the data suggests that GMFB is not only required for normal development of GFAP fibers in the zebrafish telencephalon, but also promotes reactive gliosis after TBI. Our findings provide novel information to help better understand the reactive gliosis process following TBI.
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