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The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice
Zinc (Zn(2+)) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn(2+) levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn(2+) affects synaptic plasticity and...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021411/ https://www.ncbi.nlm.nih.gov/pubmed/29950603 http://dx.doi.org/10.1038/s41598-018-28083-9 |
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author | Frazzini, Valerio Granzotto, Alberto Bomba, Manuela Massetti, Noemi Castelli, Vanessa d’Aurora, Marco Punzi, Miriam Iorio, Mariangela Mosca, Alessandra Delli Pizzi, Stefano Gatta, Valentina Cimini, Annamaria Sensi, Stefano L. |
author_facet | Frazzini, Valerio Granzotto, Alberto Bomba, Manuela Massetti, Noemi Castelli, Vanessa d’Aurora, Marco Punzi, Miriam Iorio, Mariangela Mosca, Alessandra Delli Pizzi, Stefano Gatta, Valentina Cimini, Annamaria Sensi, Stefano L. |
author_sort | Frazzini, Valerio |
collection | PubMed |
description | Zinc (Zn(2+)) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn(2+) levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn(2+) affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn(2+) levels, we employed the Zn(2+) (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signaling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn(2+) was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo. Our study highlights the importance of choosing “when”, “where”, and “how much” in the modulation of brain Zn(2+) levels. Our findings confirm the importance of targeting Zn(2+) as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn(2+) availability upon the early stages of development. |
format | Online Article Text |
id | pubmed-6021411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60214112018-07-06 The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice Frazzini, Valerio Granzotto, Alberto Bomba, Manuela Massetti, Noemi Castelli, Vanessa d’Aurora, Marco Punzi, Miriam Iorio, Mariangela Mosca, Alessandra Delli Pizzi, Stefano Gatta, Valentina Cimini, Annamaria Sensi, Stefano L. Sci Rep Article Zinc (Zn(2+)) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn(2+) levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn(2+) affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn(2+) levels, we employed the Zn(2+) (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signaling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn(2+) was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo. Our study highlights the importance of choosing “when”, “where”, and “how much” in the modulation of brain Zn(2+) levels. Our findings confirm the importance of targeting Zn(2+) as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn(2+) availability upon the early stages of development. Nature Publishing Group UK 2018-06-27 /pmc/articles/PMC6021411/ /pubmed/29950603 http://dx.doi.org/10.1038/s41598-018-28083-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Frazzini, Valerio Granzotto, Alberto Bomba, Manuela Massetti, Noemi Castelli, Vanessa d’Aurora, Marco Punzi, Miriam Iorio, Mariangela Mosca, Alessandra Delli Pizzi, Stefano Gatta, Valentina Cimini, Annamaria Sensi, Stefano L. The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title | The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title_full | The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title_fullStr | The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title_full_unstemmed | The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title_short | The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice |
title_sort | pharmacological perturbation of brain zinc impairs bdnf-related signaling and the cognitive performances of young mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021411/ https://www.ncbi.nlm.nih.gov/pubmed/29950603 http://dx.doi.org/10.1038/s41598-018-28083-9 |
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