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Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice
Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956889/ https://www.ncbi.nlm.nih.gov/pubmed/36833213 http://dx.doi.org/10.3390/genes14020285 |
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author | Syding, Linn Amanda Kubik-Zahorodna, Agnieszka Reguera, David Pajuelo Nickl, Petr Hruskova, Bohdana Kralikova, Michaela Kopkanova, Jana Novosadova, Vendula Kasparek, Petr Prochazka, Jan Rozman, Jan Turecek, Rostislav Sedlacek, Radislav |
author_facet | Syding, Linn Amanda Kubik-Zahorodna, Agnieszka Reguera, David Pajuelo Nickl, Petr Hruskova, Bohdana Kralikova, Michaela Kopkanova, Jana Novosadova, Vendula Kasparek, Petr Prochazka, Jan Rozman, Jan Turecek, Rostislav Sedlacek, Radislav |
author_sort | Syding, Linn Amanda |
collection | PubMed |
description | Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and there are knowledge gaps regarding its regulation. It is known that the HPA axis is under GABAergic control, but the contribution of the individual subunits of the GABA receptor is largely unknown. In this study, we investigated the relationship between the α5 subunit and corticosterone levels in a new mouse model deficient for Gabra5, which is known to be linked to anxiety disorders in humans and phenologs observed in mice. We observed decreased rearing behavior, suggesting lower anxiety in the Gabra5(−/−) animals; however, such a phenotype was absent in the open field and elevated plus maze tests. In addition to decreased rearing behavior, we also found decreased levels of fecal corticosterone metabolites in Gabra5(−/−) mice indicating a lowered stress response. Moreover, based on the electrophysiological recordings where we observed a hyperpolarized state of hippocampal neurons, we hypothesize that the constitutive ablation of the Gabra5 gene leads to functional compensation with other channels or GABA receptor subunits in this model. |
format | Online Article Text |
id | pubmed-9956889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99568892023-02-25 Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice Syding, Linn Amanda Kubik-Zahorodna, Agnieszka Reguera, David Pajuelo Nickl, Petr Hruskova, Bohdana Kralikova, Michaela Kopkanova, Jana Novosadova, Vendula Kasparek, Petr Prochazka, Jan Rozman, Jan Turecek, Rostislav Sedlacek, Radislav Genes (Basel) Article Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and there are knowledge gaps regarding its regulation. It is known that the HPA axis is under GABAergic control, but the contribution of the individual subunits of the GABA receptor is largely unknown. In this study, we investigated the relationship between the α5 subunit and corticosterone levels in a new mouse model deficient for Gabra5, which is known to be linked to anxiety disorders in humans and phenologs observed in mice. We observed decreased rearing behavior, suggesting lower anxiety in the Gabra5(−/−) animals; however, such a phenotype was absent in the open field and elevated plus maze tests. In addition to decreased rearing behavior, we also found decreased levels of fecal corticosterone metabolites in Gabra5(−/−) mice indicating a lowered stress response. Moreover, based on the electrophysiological recordings where we observed a hyperpolarized state of hippocampal neurons, we hypothesize that the constitutive ablation of the Gabra5 gene leads to functional compensation with other channels or GABA receptor subunits in this model. MDPI 2023-01-21 /pmc/articles/PMC9956889/ /pubmed/36833213 http://dx.doi.org/10.3390/genes14020285 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Syding, Linn Amanda Kubik-Zahorodna, Agnieszka Reguera, David Pajuelo Nickl, Petr Hruskova, Bohdana Kralikova, Michaela Kopkanova, Jana Novosadova, Vendula Kasparek, Petr Prochazka, Jan Rozman, Jan Turecek, Rostislav Sedlacek, Radislav Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title | Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title_full | Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title_fullStr | Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title_full_unstemmed | Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title_short | Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice |
title_sort | ablation of gabra5 influences corticosterone levels and anxiety-like behavior in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956889/ https://www.ncbi.nlm.nih.gov/pubmed/36833213 http://dx.doi.org/10.3390/genes14020285 |
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