Decreased Brain Zinc Availability Reduces Hippocampal Neurogenesis in Mice and Rats
Open Access
- 17 June 2009
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 29 (9), 1579-1588
- https://doi.org/10.1038/jcbfm.2009.80
Abstract
In the adult brain, neurogenesis occurs in the subgranular zone of the dentate gyrus (DG), where high levels of vesicular zinc are localized in the presynaptic terminals. To determine whether zinc has a role in modulating hippocampal neurogenesis under normal or pathologic conditions, we manipulated the level of vesicular zinc experimentally. To reduce hippocampal vesicular zinc, rats were either fed a zinc-deficient diet or treated with a zinc chelator, clioquinol (CQ). The number of progenitor cells and immature neurons was decreased significantly in the DG after 6 weeks of dietary zinc deprivation. Conversely, the number of progenitor cells and immature neurons was restored after a 2-week reversal to a normal zinc-containing diet. Similarly, a 1-week treatment with the zinc chelator, CQ, reduced the number of progenitor cells. The results of our previous study showed that hypoglycemia increased hippocampal neurogenesis. This study shows that zinc chelation reduced hypoglycemia-induced progenitor cell proliferation and neurogenesis. Finally, the role of vesicular zinc on neurogenesis was further assessed in zinc transporter 3 (ZnT3) gene deleted mice. Zinc transporter 3 knockout (KO) mice had significantly fewer proliferating progenitor cells and immature neurons after hypoglycemia. Our data provide converging evidence in support of the essential role zinc has in modulating hippocampal neurogenesis.Keywords
This publication has 39 references indexed in Scilit:
- Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanismsBrain Research, 2008
- Zinc-specific Autometallographic In Vivo Selenium Methods: Tracing of Zinc-enriched (ZEN) Terminals, ZEN Pathways, and Pools of Zinc Ions in a Multitude of Other ZEN CellsJournal of Histochemistry & Cytochemistry, 2005
- Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT 3 geneProceedings of the National Academy of Sciences of the United States of America, 1999
- Translocation of zinc may contribute to seizure-induced death of neuronsBrain Research, 1989
- Neurobiology of Zinc and Zinc-Containing NeuronsInternational Review of Neurobiology, 1989
- A quinoline fluorescence method for visualizing and assaying the histochemically reactive zinc (bouton zinc) in the brainJournal of Neuroscience Methods, 1987
- Ultrastructural autometallography: a method for silver amplification of catalytic metals.Journal of Histochemistry & Cytochemistry, 1985
- Hypoglycemic Brain Injury in the Rat: Correlation of Density of Brain Damage with the EEG Isoelectric Time: A Quantitative StudyDiabetes, 1984
- Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. I. Impaired acquisition of granule cellsBrain Research, 1983
- Exogenous selenium in the brainHistochemistry and Cell Biology, 1982