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Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice

Exposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in wor...

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Autores principales: Dominguez, Gaelle, Henkous, Nadia, Prevot, Thomas, David, Vincent, Guillou, Jean-Louis, Belzung, Catherine, Mons, Nicole, Béracochéa, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607320/
https://www.ncbi.nlm.nih.gov/pubmed/31309134
http://dx.doi.org/10.1016/j.ynstr.2019.100161
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author Dominguez, Gaelle
Henkous, Nadia
Prevot, Thomas
David, Vincent
Guillou, Jean-Louis
Belzung, Catherine
Mons, Nicole
Béracochéa, Daniel
author_facet Dominguez, Gaelle
Henkous, Nadia
Prevot, Thomas
David, Vincent
Guillou, Jean-Louis
Belzung, Catherine
Mons, Nicole
Béracochéa, Daniel
author_sort Dominguez, Gaelle
collection PubMed
description Exposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in working memory (WM), a task which heavily relies on functional interactions between the medial prefrontal cortex (PFC) and the dorsal hippocampus (dHPC). However, it is unknown whether stress-induced increases in plasma corticosterone mirror corticosterone levels in specific brain regions critical for WM. After a 6 week-UCMS exposure, C57BL/6 J male mice exhibited increased anxiety- and depressive-like behaviors when measured one week later and displayed WM impairments timely associated with increased plasma corticosterone response. In chronically stressed mice, basal phosphorylated/activated CREB (pCREB) was markedly increased in the PFC and the CA1 area of the dHPC and WM testing did not elicit any further increase in pCREB in the two regions. Using microdialysis samples from freely-moving mice, we found that WM testing co-occurred with a rapid and sustained increase in corticosterone response in the PFC while there was a late, non-significant rise of corticosterone in the dHPC. The results also show that non-stressed mice injected with corticosterone (2 mg/kg i.p.) before WM testing displayed behavioral and molecular alterations similar to those observed in stressed animals while a pre-WM testing metyrapone injection (35 mg/kg i.p.), a corticosterone synthesis inhibitor, prevented the effects of UCMS exposure. Overall, the abnormal regional increase of corticosterone concentrations mainly in the PFC emerges as a key factor of enduring WM dysfunctions in UCMS-treated animals.
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spelling pubmed-66073202019-07-15 Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice Dominguez, Gaelle Henkous, Nadia Prevot, Thomas David, Vincent Guillou, Jean-Louis Belzung, Catherine Mons, Nicole Béracochéa, Daniel Neurobiol Stress Original Research Article Exposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in working memory (WM), a task which heavily relies on functional interactions between the medial prefrontal cortex (PFC) and the dorsal hippocampus (dHPC). However, it is unknown whether stress-induced increases in plasma corticosterone mirror corticosterone levels in specific brain regions critical for WM. After a 6 week-UCMS exposure, C57BL/6 J male mice exhibited increased anxiety- and depressive-like behaviors when measured one week later and displayed WM impairments timely associated with increased plasma corticosterone response. In chronically stressed mice, basal phosphorylated/activated CREB (pCREB) was markedly increased in the PFC and the CA1 area of the dHPC and WM testing did not elicit any further increase in pCREB in the two regions. Using microdialysis samples from freely-moving mice, we found that WM testing co-occurred with a rapid and sustained increase in corticosterone response in the PFC while there was a late, non-significant rise of corticosterone in the dHPC. The results also show that non-stressed mice injected with corticosterone (2 mg/kg i.p.) before WM testing displayed behavioral and molecular alterations similar to those observed in stressed animals while a pre-WM testing metyrapone injection (35 mg/kg i.p.), a corticosterone synthesis inhibitor, prevented the effects of UCMS exposure. Overall, the abnormal regional increase of corticosterone concentrations mainly in the PFC emerges as a key factor of enduring WM dysfunctions in UCMS-treated animals. Elsevier 2019-04-04 /pmc/articles/PMC6607320/ /pubmed/31309134 http://dx.doi.org/10.1016/j.ynstr.2019.100161 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research Article
Dominguez, Gaelle
Henkous, Nadia
Prevot, Thomas
David, Vincent
Guillou, Jean-Louis
Belzung, Catherine
Mons, Nicole
Béracochéa, Daniel
Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title_full Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title_fullStr Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title_full_unstemmed Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title_short Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
title_sort sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607320/
https://www.ncbi.nlm.nih.gov/pubmed/31309134
http://dx.doi.org/10.1016/j.ynstr.2019.100161
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