Role of C/EBPβ transcription factor in adult hippocampal neurogenesis.
Role of C/EBPβ transcription factor in adult hippocampal neurogenesis.
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DOI：
10.1371/journal.pone.0024842
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Perez-Castillo A
中科院分区：
文献类型：
--
作者：
Cortes-Canteli M;Aguilar-Morante D;Sanz-Sancristobal M;Megias D;Santos A;Perez-Castillo A
海马齿状回是成人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）在成年小鼠海马齿状回的颗粒层中表达。考虑到C/EBPβ在巩固长期记忆中的重要作用，海马中新生神经元有助于学习和记忆过程的事实，以及我们小组先前证明的该转录因子在调节神经元分化中的作用，我们推测该转录因子可以调节大脑该区域的干/祖细胞。在这里，我们使用 C/EBPβ 敲除小鼠证明，在成年大脑海马中增殖的新生细胞子集中观察到 C/EBPβ 表达。缺乏 C/EBPβ 的小鼠海马中新生细胞的存活率降低，分化为神经元的细胞数量减少，齿状回颗粒下区增殖的细胞数量减少。这些结果在体外得到了进一步证实。与野生型小鼠的神经球相比，缺乏 C/EBPβ 的成年小鼠的神经球培养物的增殖和神经元分化较少。总之，利用体内和体外策略，我们已经确定 C/EBPβ 在成年小鼠海马中产生的新神经元的增殖和存活中发挥着关键作用。我们的结果支持 C/EBPβ 在成人海马神经发生过程中的新作用，为控制该大脑区域神经发生的机制提供了新的见解。
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. 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. 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.
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