NEIL3 influences adult neurogenesis and behavioral pattern separation via WNT signaling
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.
Authors
- Andreas Abentung (ORCID: https://orcid.org/0000-0003-4541-7865)
- Anna Maria Bugaj (ORCID: https://orcid.org/0000-0001-5473-047X)
- Magnar Bjørås (ORCID: https://orcid.org/0000-0001-8759-1170)
- Amilcar Reis
- Veslemøy Rolseth (ORCID: https://orcid.org/0000-0002-6240-7944)
- Nicolas Kunath (ORCID: https://orcid.org/0000-0002-7641-511X)
- Rajikala Suganthan
- Katja Scheffler (ORCID: https://orcid.org/0000-0002-1734-7807)
- Ana Beatriz Aroeira Soares (ORCID: https://orcid.org/0009-0001-8869-7943)
- Marion Silvana Fernández-Berrocal (ORCID: https://orcid.org/0000-0002-5839-9355)
- Lars Eide (ORCID: https://orcid.org/0000-0003-3948-5183)
- Richardson Naves Leão (ORCID: https://orcid.org/0000-0001-8496-1965)
- Arthur S. C. França (ORCID: https://orcid.org/0000-0002-5836-1672)
- Anna Kuśnierczyk (ORCID: https://orcid.org/0000-0003-3517-3481)
- Jing Ye (ORCID: https://orcid.org/0009-0008-9262-4916)
Institutions
- Uppsala University (SE)
- Oslo University Hospital (NO)
- University of Oslo (NO)
- Norwegian University of Science and Technology (NO)
- Universidade Federal do Rio Grande do Norte (BR)
- St Olav's University Hospital (NO)
Publication Details
- Journal
- Cellular and Molecular Life Sciences
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1007/s00018-025-05629-5
- Citations
- 3
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 5.45
Funders
- Norges Forskningsråd