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Radiation-induced impairment of optic nerve axonal transport in tree shrews and rats monitored by longitudinal manganese-enhanced MRI.
NeuroToxicology ( IF 3.4 ) Pub Date : 2020-01-24 , DOI: 10.1016/j.neuro.2020.01.008
Jun Yang 1 , Qinqing Li 1 , Dan Han 2 , Chengde Liao 1 , Pengfei Wang 3 , Jingyan Gao 4 , Zeyan Xu 1 , Yifan Liu 1
Affiliation  

PURPOSE Radiation-induced optic neuropathy (RION) is a serious complication that occurs after radiation therapy of tumors in the vicinity of the optic nerve, yet its mechanism and imaging features are poorly understood. In this study, we employed manganese-enhanced MRI (MEMRI) to assess optic nerve axonal transport in tree shrews and rats after irradiation. MATERIALS AND METHODS A comparison of normal visual projections in tree shrews and rats was conducted by intravitreal MnCl2 injection followed by MRI. Adult male tree shrews and rats received a total dose of 20 Gy delivered in two fractions (10 Gy per fraction) within 5 days. Longitudinal MEMRI was conducted 5, 10, 20 and 30 weeks after radiation. At the end of observation, motor proteins involved in axonal transport were detected by western blotting, and the axon cytoskeleton was assessed by immunofluorescence. RESULTS The eyeballs, lens sizes, vitreous volumes, optic nerves and superior colliculi of tree shrews were significantly larger than those of rats on MEMRI (P < 0.05). The Mn2+-enhancement of the optic nerve showed no significant changes at 5 and 10 weeks (P > 0.05) but decreased gradually from 20 to 30 weeks postirradiation (P < 0.05). The enhancement of the superior colliculus gradually decreased from 5 weeks to 30 weeks, and the decrease was most significant at 30 weeks (P < 0.05). The levels of the motor proteins cytoplasmic dynein-1, kinesin-1 and kinesin-2 in the experimental group were significantly decreased (P < 0.05). The immunofluorescence results showed that the α-tubulin, β-tubulin and SMI 31 levels in the experimental groups and control groups were not significantly different (P > 0.05). CONCLUSION Tree shrews show great advantages in visual neuroscience research involving MEMRI. The main cause of the decline in axonal transport in RION is an insufficient level of motor protein rather than damage to the axonal cytoskeletal structure. Longitudinal MEMRI can be used to detect changes in axonal transport function and to observe the relatively intact axon structure from the early to late stages after radiation administration.

中文翻译:

纵向锰增强MRI监测树rats和大鼠的辐射诱发视神经轴突运输障碍。

目的辐射诱发的视神经病变(RION)是在视神经附近的肿瘤进行放射治疗后发生的严重并发症,但对其机理和影像学特征了解甚少。在这项研究中,我们采用锰增强MRI(MEMRI)来评估树sh和大鼠在辐照后的视神经轴突运输。材料与方法通过玻璃体内注射MnCl2,然后进行MRI,对树sh和大鼠的正常视觉投影进行比较。成年雄性树sh和大鼠在5天内分两部分(每部分10 Gy)递送了20 Gy的总剂量。放疗后5、10、20和30周进行纵向MEMRI。在观察结束时,通过蛋白质印迹检测到了参与轴突运输的运动蛋白,并通过免疫荧光评估轴突的细胞骨架。结果树sh的眼球,晶状体大小,玻璃体体积,视神经和上丘肌明显大于大鼠的MEMRI(P <0.05)。视神经的Mn2 +增强在5周和10周时无明显变化(P> 0.05),但在照射后20至30周逐渐降低(P <0.05)。上丘的增强逐渐从5周减少到30周,并且在30周时下降最为明显(P <0.05)。实验组运动蛋白胞质中的dynein-1,kinesin-1和kinesin-2水平明显降低(P <0.05)。免疫荧光结果表明,α-微管蛋白,实验组和对照组的β-微管蛋白和SMI 31水平无显着性差异(P> 0.05)。结论树sh在涉及MEMRI的视觉神经科学研究中显示出巨大的优势。RION中轴突运输减少的主要原因是运动蛋白水平不足,而不是轴突细胞骨架结构受损。纵向MEMRI可用于检测轴突运输功能的变化,并观察放射治疗后早期到晚期相对完整的轴突结构。
更新日期:2020-01-24
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