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Figure 1. Iron as a dynamic regulator of neurogenesis and stress-induced plasticity. Iron plays an indispensable role throughout CNS neurodevelopment.
(1) During adult neurogenesis, neural stem cells and neural progenitor cells in the hippocampus regulate intracellular iron homeostasis via SLC22A17. SLC22A17-associated endosomal iron export contributes to the stabilization of cellular states and influences cell fate decisions during the neurogenic process; (2) Under conditions of social isolation, neurons in the vHIP exhibit increased TfR-mediated iron uptake. Through interactions with α-synuclein, iron modulates the stability of the SNARE complex, leading to enhanced presynaptic glutamate release. This process induces synaptic remodeling, reflected by an increased density of dendritic spines; (3) Across neurodevelopment, coordinated iron influx and efflux mediated by the SLC22A17/TfR1 axis contribute to the maintenance of brain iron homeostasis. CNS iron balance, in turn, exerts stage-dependent effects on multiple temporal windows of neurodevelopment [Created in BioRender. 2, 1. (2026) https://BioRender.com/6pg0954].