Pérez-Montes Cristina, Jiménez-Cubides Jhoana Paola, Velasco Almudena, Arévalo Rosario, Santos-Ledo Adrián, García-Macia Marina
Instituto de Neurociencias de Castilla y León (INCyL), 37007 Salamanca, Spain.
Department of Human Anatomy and Histology, Universidad de Salamanca, 37007 Salamanca, Spain.
Antioxidants (Basel). 2023 Nov 22;12(12):2026. doi: 10.3390/antiox12122026.
Zebrafish () present continuous growth and regenerate many parts of their body after an injury. Fish oligodendrocytes, microglia and astrocytes support the formation of new connections producing effective regeneration of the central nervous system after a lesion. To understand the role of oligodendrocytes and the signals that mediate regeneration, we use the well-established optic nerve (ON) crush model. We also used fluorescent transgenic lines to label fully differentiated oligodendrocytes. To quench the effect of reactive oxygen species (ROS), we used the endogenous antioxidant melatonin. Using these tools, we measured ROS production by flow cytometry and explored the regeneration of the optic tectum (OT), the response of oligodendrocytes and their mitochondria by confocal microscopy and Western blot. ROS are produced by oligodendrocytes 3 h after injury and JNK activity is triggered. Concomitantly, there is a decrease in the number of fully differentiated oligodendrocytes in the OT and in their mitochondrial population. By 24 h, oligodendrocytes partially recover. Exposure to melatonin blocks the changes observed in these oligodendrocytes at 3 h and increases their number and their mitochondrial populations after 24 h. Melatonin also blocks JNK upregulation and induces aberrant neuronal differentiation in the OT. In conclusion, a proper balance of ROS is necessary during visual system regeneration and exposure to melatonin has a detrimental impact.
斑马鱼持续生长,受伤后身体的许多部位能够再生。鱼类少突胶质细胞、小胶质细胞和星形胶质细胞支持新连接的形成,从而在损伤后实现中枢神经系统的有效再生。为了了解少突胶质细胞的作用以及介导再生的信号,我们使用了成熟的视神经挤压模型。我们还使用荧光转基因品系标记完全分化的少突胶质细胞。为了消除活性氧(ROS)的影响,我们使用了内源性抗氧化剂褪黑素。利用这些工具,我们通过流式细胞术测量ROS的产生,并通过共聚焦显微镜和蛋白质免疫印迹法探索视顶盖(OT)的再生、少突胶质细胞及其线粒体的反应。损伤后3小时,少突胶质细胞产生ROS并触发JNK活性。与此同时,OT中完全分化的少突胶质细胞数量及其线粒体数量减少。到24小时时,少突胶质细胞部分恢复。褪黑素处理可阻止这些少突胶质细胞在3小时时观察到的变化,并在24小时后增加其数量及其线粒体数量。褪黑素还可阻止JNK上调,并在OT中诱导异常神经元分化。总之,在视觉系统再生过程中,ROS的适当平衡是必要的,而褪黑素处理具有有害影响。