Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institue of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Life Sci. 2020 Aug 1;254:117755. doi: 10.1016/j.lfs.2020.117755. Epub 2020 May 8.
Efficient memory formation in rodents depends on adult neurogenesis in the subgranular zone of the hippocampus, and mounting evidence suggests that deficiencies in initiating repair of oxidatively induced DNA damage may impair neurogenesis. Hence, we aimed to determine whether loss of the DNA glycosylase, endonuclease VIII-like 1 (Neil1), affects hippocampal neurogenesis and memory performance in young-adult mice.
Eight-week-old male wild-type and Neil1-deficient (Neil1) mice were treated with bromodeoxyuridine to track neuronal proliferation and differentiation. A neurosphere formation assay was further used to measure neuroprogenitor proliferative capacity. Hippocampus-related memory functions were assessed with Y-maze spontaneous alternation and novel object recognition tests.
Young-adult male Neil1 mice exhibited diminished adult hippocampal neurogenesis in the dentate gyrus, probably as a result of poor survival of newly proliferated neurons. Furthermore, the Y-maze spontaneous alternation and novel object recognition tests respectively revealed that Neil1 deficiency impairs spatial and non-spatial hippocampus-related memory functions. We also found that expression of p53, a central regulator of apoptosis, was upregulated in the dentate gyrus of Neil1 mice, while the level of β-catenin, a key cell survival molecule, was downregulated.
The DNA glycosylase, Neil1, promotes successful hippocampal neurogenesis and learning and memory in young-adult mice.
在啮齿动物中，有效的记忆形成依赖于海马颗粒下区的成年神经发生，越来越多的证据表明，启动氧化诱导的 DNA 损伤修复的缺陷可能会损害神经发生。因此，我们旨在确定 DNA 糖苷酶内切核酸酶 VIII 样 1（Neil1）的缺失是否会影响年轻成年小鼠的海马神经发生和记忆表现。
八周龄雄性野生型和 Neil1 缺陷型（Neil1）小鼠用溴脱氧尿苷处理以追踪神经元增殖和分化。进一步进行神经球形成测定以测量神经祖细胞的增殖能力。使用 Y 迷宫自发交替和新物体识别测试评估海马相关记忆功能。
年轻成年雄性 Neil1 小鼠在齿状回中表现出成年海马神经发生减少，可能是由于新增殖神经元的存活不良所致。此外，Y 迷宫自发交替和新物体识别测试分别表明，Neil1 缺陷会损害空间和非空间海马相关记忆功能。我们还发现，凋亡的中央调节因子 p53 在 Neil1 小鼠的齿状回中上调，而关键细胞存活分子 β-连环蛋白的水平下调。
DNA 糖苷酶 Neil1 促进年轻成年小鼠海马神经发生和学习记忆成功。
