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Therefore, we sought to investigate the idea that vesicular zinc plays a role as a modulator of hippocampal adult neurogenesis. Here, we used ZnT3\u2212\/\u2212 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\u2212\/\u2212 mice. Therefore, the present study suggests that ZnT3 and vesicular zinc are essential for adult hippocampal neurogenesis.<\/jats:p>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.1002\/stem.3194","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T01:24:55Z","timestamp":1588123495000},"page":"994-1006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus"],"prefix":"10.1093","volume":"38","author":[{"given":"Bo Young","family":"Choi","sequence":"first","affiliation":[{"name":"1 Department of Physiology, Hallym University College of Medicine, Chuncheon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Ki","family":"Hong","sequence":"additional","affiliation":[{"name":"1 Department of Physiology, Hallym University College of Medicine, Chuncheon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hyun","family":"Jeong","sequence":"additional","affiliation":[{"name":"1 Department of Physiology, Hallym University College of Medicine, Chuncheon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"1 Department of Physiology, Hallym University College of Medicine, Chuncheon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Young","family":"Koh","sequence":"additional","affiliation":[{"name":"2 Department of Neurology, University of Ulsan College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-579X","authenticated-orcid":false,"given":"Sang Won","family":"Suh","sequence":"additional","affiliation":[{"name":"1 Department of Physiology, Hallym 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