Instituto de Investigaciones Biomedicas "Alberto Sols", Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, Madrid, Spain.
PLoS One. 2011;6(10):e24842. doi: 10.1371/journal.pone.0024842. Epub 2011 Oct 7.
The dentate gyrus of the hippocampus is one of the regions in which neurogenesis takes place in the adult brain. We have previously demonstrated that CCAAT/enhancer binding protein β (C/EBPβ) is expressed in the granular layer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBPβ in the consolidation of long term memory, the fact that newborn neurons in the hippocampus contribute to learning and memory processes, and the role of this transcription factor, previously demonstrated by our group, in regulating neuronal differentiation, we speculated that this transcription factor could regulate stem/progenitor cells in this region of the brain.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we show, using C/EBPβ knockout mice, that C/EBPβ expression is observed in the subset of newborn cells that proliferate in the hippocampus of the adult brain. Mice lacking C/EBPβ present reduced survival of newborn cells in the hippocampus, a decrease in the number of these cells that differentiate into neurons and a diminished number of cells that are proliferating in the subgranular zone of the dentate gyrus. These results were further confirmed in vitro. Neurosphere cultures from adult mice deficient in C/EBPβ present less proliferation and neuronal differentiation than neurospheres derived from wild type mice.
CONCLUSIONS/SIGNIFICANCE: In summary, using in vivo and in vitro strategies, we have identified C/EBPβ as a key player in the proliferation and survival of the new neurons produced in the adult mouse hippocampus. Our results support a novel role of C/EBPβ in the processes of adult hippocampal neurogenesis, providing new insights into the mechanisms that control neurogenesis in this region of the brain.
海马回的齿状回是成年大脑中发生神经发生的区域之一。我们之前已经证明，CCAAT/增强子结合蛋白β（C/EBPβ）在成年小鼠海马回的颗粒层中表达。考虑到 C/EBPβ在长期记忆巩固中的重要作用，海马回中的新生神经元对学习和记忆过程有贡献，以及该转录因子在调节神经元分化方面的作用，先前由我们小组证明，我们推测该转录因子可以调节大脑这一区域的干细胞/祖细胞。
方法/主要发现：在这里，我们使用 C/EBPβ 敲除小鼠表明，C/EBPβ 的表达在成年大脑海马回中增殖的新生细胞亚群中观察到。缺乏 C/EBPβ 的小鼠表现出海马回中新生细胞存活率降低，这些细胞分化为神经元的数量减少，以及在齿状回颗粒下层增殖的细胞数量减少。这些结果在体外进一步得到证实。缺乏 C/EBPβ 的成年小鼠的神经球培养物比来自野生型小鼠的神经球增殖和神经元分化更少。
结论/意义：总之，我们使用体内和体外策略确定 C/EBPβ 是成年小鼠海马回中产生的新神经元增殖和存活的关键因素。我们的结果支持 C/EBPβ 在成年海马神经发生过程中的新作用，为控制该脑区神经发生的机制提供了新的见解。
