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Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures

Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse su...

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Autores principales: Kurek, Anna, Kucharczyk, Mateusz, Detka, Jan, Ślusarczyk, Joanna, Trojan, Ewa, Głombik, Katarzyna, Bojarski, Bartosz, Ludwikowska, Agnieszka, Lasoń, Władysław, Budziszewska, Bogusława
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947107/
https://www.ncbi.nlm.nih.gov/pubmed/27189478
http://dx.doi.org/10.1007/s12640-016-9630-8
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author Kurek, Anna
Kucharczyk, Mateusz
Detka, Jan
Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Bojarski, Bartosz
Ludwikowska, Agnieszka
Lasoń, Władysław
Budziszewska, Bogusława
author_facet Kurek, Anna
Kucharczyk, Mateusz
Detka, Jan
Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Bojarski, Bartosz
Ludwikowska, Agnieszka
Lasoń, Władysław
Budziszewska, Bogusława
author_sort Kurek, Anna
collection PubMed
description Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 μM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 μM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone’s effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-α expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-α remained high. The present study showed that in stress-like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro-apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-α may be connected with the adverse effects of corticosterone on brain cell viability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12640-016-9630-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-49471072016-07-26 Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures Kurek, Anna Kucharczyk, Mateusz Detka, Jan Ślusarczyk, Joanna Trojan, Ewa Głombik, Katarzyna Bojarski, Bartosz Ludwikowska, Agnieszka Lasoń, Władysław Budziszewska, Bogusława Neurotox Res Original Article Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 μM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 μM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone’s effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-α expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-α remained high. The present study showed that in stress-like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro-apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-α may be connected with the adverse effects of corticosterone on brain cell viability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12640-016-9630-8) contains supplementary material, which is available to authorized users. Springer US 2016-05-17 2016 /pmc/articles/PMC4947107/ /pubmed/27189478 http://dx.doi.org/10.1007/s12640-016-9630-8 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Original Article
Kurek, Anna
Kucharczyk, Mateusz
Detka, Jan
Ślusarczyk, Joanna
Trojan, Ewa
Głombik, Katarzyna
Bojarski, Bartosz
Ludwikowska, Agnieszka
Lasoń, Władysław
Budziszewska, Bogusława
Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title_full Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title_fullStr Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title_full_unstemmed Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title_short Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures
title_sort pro-apoptotic action of corticosterone in hippocampal organotypic cultures
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947107/
https://www.ncbi.nlm.nih.gov/pubmed/27189478
http://dx.doi.org/10.1007/s12640-016-9630-8
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