In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task. Mice deficient in LCN2 present an increase in the NSCs population, as a consequence of a G0/G1 cell cycle arrest induced by increased endogenous oxidative stress. Of notice, supplementation with the iron-chelating agent deferoxamine rescues NSCs oxidative stress, promotes cell cycle progression and improves contextual fear conditioning. LCN2 is, therefore, a novel key modulator of neurogenesis that, through iron, controls NSCs cell cycle progression and death, self-renewal, proliferation and differentiation and, ultimately, hippocampal function.

中文翻译：

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Lipocalin-2调节成人神经发生和上下文区分行为。

在成年哺乳动物的大脑中，新生的颗粒细胞不断整合到海马回路中，这一过程的微调对于海马功能很重要。因此，确定控制成年神经干细胞（NSC）维持，分化和整合的因素至关重要。在这里，我们表明铁运输蛋白lipocalin-2（LCN2）的删除诱导了NSCs增殖和承诺的赤字，对海马依赖的上下文恐惧判别任务的影响。缺乏LCN2的小鼠由于增加的内源性氧化应激诱导了G0 / G1细胞周期停滞，从而导致NSCs种群增加。值得注意的是，补充铁螯合剂去铁胺可以挽救NSC的氧化应激，促进细胞周期进程并改善情境恐惧条件。因此，LCN2是神经发生的新型关键调节剂，它通过铁控制NSC的细胞周期进程和死亡，自我更新，增殖和分化，并最终控制海马功能。