101. Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus
- Author
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Sang Won Suh, Jeong Hyun Jeong, Bo Eun Lee, Bo Young Choi, Jae-Young Koh, and Dae Ki Hong
- Subjects
Male ,0301 basic medicine ,hippocampus ,Neurogenesis ,Hippocampus ,Hippocampal formation ,Biology ,Subgranular zone ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Chlorides ,Neuroblast ,n‐acetyl cysteine ,medicine ,Animals ,Cognitive decline ,Progenitor cell ,Cation Transport Proteins ,Cell Proliferation ,Neurons ,Dentate gyrus ,zinc ,Cell Differentiation ,Cell Biology ,Acetylcysteine ,Cell biology ,Mice, Inbred C57BL ,Tissue‐specific Stem Cells ,adult neurogenesis ,030104 developmental biology ,medicine.anatomical_structure ,Zinc Compounds ,zinc transporter 3 ,Molecular Medicine ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The subgranular zone of the dentate gyrus is a subregion of the hippocampus that has two uniquely defining features; it is one of the most active sites of adult neurogenesis as well as the location where the highest concentrations of synaptic zinc are found, the mossy fiber terminals. Therefore, we sought to investigate the idea that vesicular zinc plays a role as a modulator of hippocampal adult neurogenesis. Here, we used ZnT3 −/− mice, which are depleted of synaptic‐vesicle zinc, to test the effect of targeted deletion of this transporter on adult neurogenesis. We found that this manipulation reduced progenitor cell turnover as well as led to a marked defect in the maturation of newborn cells that survive in the DG toward a neuronal phenotype. We also investigated the effects of zinc (ZnCl2), n‐acetyl cysteine (NAC), and ZnCl2 plus 2NAC (ZN) supplement on adult hippocampal neurogenesis. Compared with ZnCl2 or NAC, administration of ZN resulted in an increase in proliferation of progenitor cells and neuroblast. ZN also rescued the ZnT3 loss‐associated reduction of neurogenesis via elevation of insulin‐like growth factor‐1 and ERK/CREB activation. Together, these findings reveal that ZnT3 plays a highly important role in maintaining adult hippocampal neurogenesis and supplementation by ZN has a beneficial effect on hippocampal neurogenesis, as well as providing a therapeutic target for enhanced neuroprotection and repair after injury as demonstrated by its ability to prevent aging‐dependent cognitive decline in ZnT3 −/− mice. Therefore, the present study suggests that ZnT3 and vesicular zinc are essential for adult hippocampal neurogenesis., This study utilized ZnT3 −/− mice with a genetic loss‐of‐function approach to investigate the consequences of vesicular zinc depletion in adult hippocampal neurogenesis. We found that ZnT3 −/− mice displayed reduced hippocampal neurogenesis under physiological conditions even at 3 months of age. We also found that administration of ZnCl2 plus 2NAC (ZN) not only reversed the ZnT3 loss‐associated reduction of neurogenesis, but also improved aging‐dependent cognitive decline in ZnT3 −/− mice.
- Published
- 2020