Fernandez-Berrocal Marion S, Reis Amilcar, Rolseth Veslemøy, Suganthan Rajikala, Kuśnierczyk Anna, França Arthur, Soares Annara Y M, Kunath Nicolas, Bugaj Anna M, Abentung Andreas, Eide Lars, Leão Richardson N, Bjørås Magnar, Scheffler Katja, Ye Jing
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491, Trondheim, Norway.
Department of Neuroscience, Uppsala University, 752 36, Uppsala, Sweden.
Cell Mol Life Sci. 2025 Mar 4;82(1):101. doi: 10.1007/s00018-025-05629-5.
Adult neurogenesis in the hippocampus, involving the generation and integration of new neurons, is essential for behavioral pattern separation, which supports accurate memory recall and cognitive plasticity. Here, we explore the role of the DNA repair protein NEIL3 in adult hippocampal neurogenesis and behavioral pattern separation. NEIL3 is required for efficient proliferation and neuronal differentiation of neonatal NSPCs and adult-born NPCs in the hippocampus following a behavioral pattern separation task. NEIL3-depleted mice exhibited a reduced preference for the novel object location, indicating a deficit in pattern separation. NEIL3-deficient adult-born neurons exhibited a significant reduction in mature-like membrane properties, indicating impaired functional maturation. Interestingly, these impairments were not associated with the decreased genomic integrity but with the altered transcriptional regulation of the Wnt signaling pathway. Given the importance of adult neurogenesis in cognitive function, targeting NEIL3 could offer therapeutic potential for addressing age-related hippocampal dysfunction and cognitive decline.
海马体中的成年神经发生，涉及新神经元的产生与整合，对于行为模式分离至关重要，行为模式分离有助于准确的记忆回忆和认知可塑性。在此，我们探究DNA修复蛋白NEIL3在成年海马体神经发生及行为模式分离中的作用。在行为模式分离任务后，NEIL3是海马体中新生神经干细胞（NSPCs）和成年新生神经前体细胞（NPCs）高效增殖及神经元分化所必需的。NEIL3缺失的小鼠对新物体位置的偏好降低，表明其在模式分离方面存在缺陷。NEIL3缺陷的成年新生神经元表现出成熟样膜特性显著降低，表明其功能成熟受损。有趣的是，这些损伤与基因组完整性降低无关，而是与Wnt信号通路转录调控改变有关。鉴于成年神经发生在认知功能中的重要性，靶向NEIL3可能为解决与年龄相关的海马体功能障碍和认知衰退提供治疗潜力。
