Zong, R., Zhang, X., Dong, X. et al. (7 more authors) (2024) Genetic deletion of zinc transporter ZnT₃ induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism. Frontiers in Molecular Neuroscience, 17. 1375925. ISSN 1662-5099
Abstract
Zinc transporter 3 (ZnT₃) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT₃ knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT₃ deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT₃ deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT₃ knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT₃ knockout mice. We hypothesize that the ZnT₃ deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Zong, Zhang, Dong, Liu, Zhang, Gao, Zhang, Ma, Gao and Gamper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | ZnT₃, zinc, dendritic plasticity, spatial memory, glycometabolis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number BBSRC (Biotechnology & Biological Sciences Research Council) BB/R02104X/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Apr 2024 10:33 |
Last Modified: | 31 May 2024 15:04 |
Published Version: | https://www.frontiersin.org/articles/10.3389/fnmol... |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fnmol.2024.1375925 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211766 |