Peer-reviewedCC BYCell stem cell
Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging
7 affiliations
- 1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Brain Research Centre, Department of Biology, School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
- 2Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
- 3Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- 4CRTD - Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden 01307, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden 01307, Germany
- 5Florey Institute of Neuroscience & Mental Health, The University of Melbourne, Melbourne, VIC 3052, Australia
- 6Brain Research Centre, Department of Biology, School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
- 7Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: [email protected]
Abstract
Adult hippocampal neurogenesis declines with age, but the stress pathways that shape neural precursor cell (NPC) survival and lineage progression remain incompletely understood. Here, we tested whether ferroptosis-related vulnerability contributes to the regulation of hippocampal NPCs and their progeny. Using in vitro assays, transcriptomic analyses, and in vivo genetic and pharmacologic perturbations, we find that NPCs show features consistent with elevated susceptibility to ferroptotic stress relative to more differentiated hippocampal populations. Reducing glutathione peroxidase 4 (GPX4) or increasing ferroptotic stress impairs neurogenesis-associated cellular and behavioral phenotypes, whereas pathway modulation improves selected outcomes in aged animals. These effects were context dependent, with distinct consequences across age and behavioral paradigms. Together, the findings support a model in which ferroptosis-related susceptibility contributes to the regulation of adult hippocampal neurogenesis and cognition.
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BibTeX
@article{zhang2026ferroptosis,
title = {{Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging}},
author = {Zhenyu Zhang and Alison Carlisle and Hamish P. Carter and Joshua Lowe and Menekşe Mutlu-Smith and Wendy Lee and Odette Leiter and Shilong Zhang and Annie Harding and Muhammed Syed and David Brici and Rupert W. Overall and Nicole Rund and Christina Steinhauer and Daniel G. Blackmore and Scott Ayton and Ashley Ian Bush and Miaona Chen and Gerd Kempermann and Sheng‐Tao Hou and Tara L. Walker},
journal = {Cell stem cell},
year = {2026},
month = may,
doi = {10.1016/j.stem.2026.04.017},
url = {https://doi.org/10.1016/j.stem.2026.04.017},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging
AU - Zhenyu Zhang
AU - Alison Carlisle
AU - Hamish P. Carter
AU - Joshua Lowe
AU - Menekşe Mutlu-Smith
AU - Wendy Lee
AU - Odette Leiter
AU - Shilong Zhang
AU - Annie Harding
AU - Muhammed Syed
AU - David Brici
AU - Rupert W. Overall
AU - Nicole Rund
AU - Christina Steinhauer
AU - Daniel G. Blackmore
AU - Scott Ayton
AU - Ashley Ian Bush
AU - Miaona Chen
AU - Gerd Kempermann
AU - Sheng‐Tao Hou
AU - Tara L. Walker
PY - 2026
DA - 2026/05/22
JO - Cell stem cell
DO - 10.1016/j.stem.2026.04.017
UR - https://doi.org/10.1016/j.stem.2026.04.017
AB - Adult hippocampal neurogenesis declines with age, but the stress pathways that shape neural precursor cell (NPC) survival and lineage progression remain incompletely understood. Here, we tested whether ferroptosis-related vulnerability contributes to the regulation of hippocampal NPCs and their progeny. Using in vitro assays, transcriptomic analyses, and in vivo genetic and pharmacologic perturbations, we find that NPCs show features consistent with elevated susceptibility to ferroptotic stress relative to more differentiated hippocampal populations. Reducing glutathione peroxidase 4 (GPX4) or increasing ferroptotic stress impairs neurogenesis-associated cellular and behavioral phenotypes, whereas pathway modulation improves selected outcomes in aged animals. These effects were context dependent, with distinct consequences across age and behavioral paradigms. Together, the findings support a model in which ferroptosis-related susceptibility contributes to the regulation of adult hippocampal neurogenesis and cognition.
SN - 1875-9777
SN - 1934-5909
ER -