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Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on?
Chloride homeostasis, the main determinant factor for the dynamic tuning of GABAergic inhibition during development, has emerged as a key element altered in a wide variety of brain disorders. Accordingly, developmental disorders such as schizophrenia, Autism Spectrum Disorder, Down syndrome, epileps...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562743/ https://www.ncbi.nlm.nih.gov/pubmed/33060559 http://dx.doi.org/10.1038/s41398-020-01027-6 |
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author | Pozzi, Davide Rasile, Marco Corradini, Irene Matteoli, Michela |
author_facet | Pozzi, Davide Rasile, Marco Corradini, Irene Matteoli, Michela |
author_sort | Pozzi, Davide |
collection | PubMed |
description | Chloride homeostasis, the main determinant factor for the dynamic tuning of GABAergic inhibition during development, has emerged as a key element altered in a wide variety of brain disorders. Accordingly, developmental disorders such as schizophrenia, Autism Spectrum Disorder, Down syndrome, epilepsy, and tuberous sclerosis complex (TSC) have been associated with alterations in the expression of genes codifying for either of the two cotransporters involved in the excitatory-to-inhibitory GABA switch, KCC2 and NKCC1. These alterations can result from environmental insults, including prenatal stress and maternal separation which share, as common molecular denominator, the elevation of pro-inflammatory cytokines. In this review we report and systemize recent research articles indicating that different perinatal environmental perturbations affect the expression of chloride transporters, delaying the developmental switch of GABA signaling, and that inflammatory cytokines, in particular interleukin 1β, may represent a key causal factor for this phenomenon. Based on literature data, we provide therefore a unifying conceptual framework, linking environmental hits with the excitatory-to-inhibitory GABA switch in the context of brain developmental disorders. |
format | Online Article Text |
id | pubmed-7562743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75627432020-10-19 Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? Pozzi, Davide Rasile, Marco Corradini, Irene Matteoli, Michela Transl Psychiatry Review Article Chloride homeostasis, the main determinant factor for the dynamic tuning of GABAergic inhibition during development, has emerged as a key element altered in a wide variety of brain disorders. Accordingly, developmental disorders such as schizophrenia, Autism Spectrum Disorder, Down syndrome, epilepsy, and tuberous sclerosis complex (TSC) have been associated with alterations in the expression of genes codifying for either of the two cotransporters involved in the excitatory-to-inhibitory GABA switch, KCC2 and NKCC1. These alterations can result from environmental insults, including prenatal stress and maternal separation which share, as common molecular denominator, the elevation of pro-inflammatory cytokines. In this review we report and systemize recent research articles indicating that different perinatal environmental perturbations affect the expression of chloride transporters, delaying the developmental switch of GABA signaling, and that inflammatory cytokines, in particular interleukin 1β, may represent a key causal factor for this phenomenon. Based on literature data, we provide therefore a unifying conceptual framework, linking environmental hits with the excitatory-to-inhibitory GABA switch in the context of brain developmental disorders. Nature Publishing Group UK 2020-10-15 /pmc/articles/PMC7562743/ /pubmed/33060559 http://dx.doi.org/10.1038/s41398-020-01027-6 Text en © The Author(s) 2020 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 | Review Article Pozzi, Davide Rasile, Marco Corradini, Irene Matteoli, Michela Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title | Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title_full | Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title_fullStr | Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title_full_unstemmed | Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title_short | Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on? |
title_sort | environmental regulation of the chloride transporter kcc2: switching inflammation off to switch the gaba on? |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562743/ https://www.ncbi.nlm.nih.gov/pubmed/33060559 http://dx.doi.org/10.1038/s41398-020-01027-6 |
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