Deutsche Forshungsgemeinschaft-Center for Regenerative Therapies Dresden-Cluster of Excellence, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
Science. 2012 Dec 7;338(6112):1353-6. doi: 10.1126/science.1228773. Epub 2012 Nov 8.
The zebrafish regenerates its brain after injury and hence is a useful model organism to study the mechanisms enabling regenerative neurogenesis, which is poorly manifested in mammals. Yet the signaling mechanisms initiating such a regenerative response in fish are unknown. Using cerebroventricular microinjection of immunogenic particles and immunosuppression assays, we showed that inflammation is required and sufficient for enhancing the proliferation of neural progenitors and subsequent neurogenesis by activating injury-induced molecular programs that can be observed after traumatic brain injury. We also identified cysteinyl leukotriene signaling as an essential component of inflammation in the regenerative process of the adult zebrafish brain. Thus, our results demonstrate that in zebrafish, in contrast to mammals, inflammation is a positive regulator of neuronal regeneration in the central nervous system.
斑马鱼在受伤后会再生其大脑,因此是研究促进神经发生的再生机制的有用模式生物,而哺乳动物的这种机制表现不佳。然而,目前尚不清楚鱼类中引发这种再生反应的信号机制。通过脑室微注射免疫原性颗粒和免疫抑制实验,我们表明炎症是必需的和充分的,它通过激活创伤性脑损伤后可观察到的损伤诱导的分子程序,增强神经祖细胞的增殖和随后的神经发生。我们还确定半胱氨酰白三烯信号作为成年斑马鱼大脑再生过程中炎症的一个重要组成部分。因此,我们的结果表明,与哺乳动物相比,在斑马鱼中,炎症是中枢神经系统神经元再生的一个正向调节因子。