Journal Article

DZNE-2026-00608

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ferroptosis susceptibility in hippocampal neural precursor cells influences neurogenesis and memory across aging.

Zhang, Z. ; Carlisle, A. K. ; Carter, H. P. ; Lowe, J. R. ; Mutlu-Smith, M. ; Lee, W. ; Leiter, O. ; Zhang, S. ; Harding, A. ; Syed, M. ; Brici, D. ; Overall, R.DZNE* ; Rund, N.DZNE* ; Steinhauer, C.DZNE* ; Blackmore, D. G. ; Ayton, S. ; Bush, A. I. ; Chen, M. ; Kempermann, G.DZNE* ; Hou, S.-T. ; Walker, T. L.

2026
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.stem.2026.04.017

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.

Keyword(s): Animals (MeSH) ; Neurogenesis (MeSH) ; Hippocampus: cytology (MeSH) ; Neural Stem Cells: metabolism (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Aging: physiology (MeSH) ; Ferroptosis (MeSH) ; Memory: physiology (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Male (MeSH) ; adult hippocampal neurogenesis ; ferroptosis ; hippocampus ; learning and memory ; lipid peroxidation ; neural precursor cell ; neural stem cell

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Contributing Institute(s):

1. Adult Neurogenesis (AG Kempermann)
2. Nuclear Architecture in Neural Plasticity and Aging (AG Toda)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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