Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
Brain Res. 2010 May 12;1330:9-19. doi: 10.1016/j.brainres.2010.03.026. Epub 2010 Mar 15.
In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5-bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi-, and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats.
除了突触重塑,新神经元的形成越来越被认为是中枢神经系统可塑性变化的重要线索。虽然所有的脊椎动物都保持着适度的神经增殖能力,但在衰老过程中,进化上较年轻的哺乳动物在这种潜力方面会显著受损。本研究表明,作为食虫动物的毛猬,其脑化指数较低,在衰老过程中其神经发生潜能惊人地得以保留。这是通过对 2 至 7 岁动物嗅球、古皮质、旧皮质和新皮质中 5-溴-2'-脱氧尿苷 (BrdU) 免疫标记的定量分析显示的。除了这些新产生的细胞,大量之前形成的未成熟神经元在成年期也存在,这一点可以通过在包括古皮质、旧皮质、伏隔核和杏仁核在内的各种前脑区域的双皮质蛋白 (DCX) 免疫染色来证明。嗅球和海马中的几个脑室相关细胞被 BrdU 和 DCX 免疫反应双重标记。然而,古皮质中的大多数 DCX 细胞可以被认为是持续存在的未成熟神经元,显然不会进入分化程序,因为双重荧光标记并不能揭示它们与许多神经元标记物的共存,而只有一小部分与泛神经元标记物 HuC/D 共表达。最后,本研究表明毛猬是研究年龄相关脑改变(例如神经发生)或缓慢退行性过程的合适实验室动物,这主要是由于与小鼠和大鼠相比,毛猬的寿命至少延长了两倍。