Division of Bio-Function Dynamics Imaging, Center for Life Science Technology, RIKEN, Kobe, Hyogo 650-0047, Japan.
Animal Resource Development Unit and Genetic Engineering Team, Center for Life Science Technology, RIKEN, Kobe, Hyogo 650-0047, Japan.
Development. 2019 Feb 18;146(4):dev168120. doi: 10.1242/dev.168120.
The self-renewal activity of neural stem cells (NSCs) has been suggested to decrease with aging, resulting in age-dependent declines in brain function, such as presbyopia and memory loss. The molecular mechanisms underlying decreases in NSC proliferation with age need to be elucidated in more detail to develop treatments that promote brain function. We have previously reported that the expression of esophageal cancer-related gene 4 () was upregulated in aged NSCs, whereas its overexpression decreased NSC proliferation, suggesting a functional relationship between Ecrg4 and NSC aging. Using Ecrg4-deficient mice in which the locus was replaced with the gene, we here show that Ecrg4 deficiency recovered the age-dependent decline in NSC proliferation and enhanced spatial learning and memory in the Morris water-maze paradigm. We demonstrate that the proliferation of Ecrg4-deficient NSCs was partly maintained by the increased expression of Foxg1. Collectively, these results determine Ecrg4 as a NSC aging factor.
神经干细胞（NSCs）的自我更新活动被认为随着年龄的增长而减少，导致与年龄相关的大脑功能下降，如老花眼和记忆力减退。需要更详细地阐明导致 NSC 增殖随年龄减少的分子机制，以开发促进大脑功能的治疗方法。我们之前曾报道过食管癌细胞相关基因 4（）在衰老的 NSCs 中表达上调，而其过表达则降低了 NSC 的增殖，表明 Ecrg4 与 NSC 衰老之间存在功能关系。在这里，我们使用缺失了 基因座并用 基因取代的 Ecrg4 缺陷型小鼠，表明 Ecrg4 缺乏可恢复 NSC 增殖随年龄增长的下降，并增强在 Morris 水迷宫范式中的空间学习和记忆。我们证明 Ecrg4 缺陷型 NSCs 的增殖部分通过 Foxg1 的表达增加来维持。总之，这些结果确定了 Ecrg4 作为 NSC 衰老因子。
