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Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala

Increasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can di...

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Autores principales: Adkins, Austin M., Colby, Emily M., Kim, Woong-Ki, Wellman, Laurie L., Sanford, Larry D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225081/
https://www.ncbi.nlm.nih.gov/pubmed/37244986
http://dx.doi.org/10.1186/s12974-023-02813-x
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author Adkins, Austin M.
Colby, Emily M.
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
author_facet Adkins, Austin M.
Colby, Emily M.
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
author_sort Adkins, Austin M.
collection PubMed
description Increasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can differentially alter inflammatory-related gene expression in brain in a region dependent manner. We have also demonstrated that the basolateral amygdala (BLA) regulates stress- and fear memory-induced alterations in sleep, and that differential sleep and immune responses in the brain to ES and IS appear to be integrated during fear conditioning and then reproduced by fear memory recall. In this study, we investigated the role of BLA in influencing regional inflammatory responses within the hippocampus (HPC) and medial prefrontal cortex (mPFC) by optogenetically stimulating or inhibiting BLA in male C57BL/6 mice during footshock stress in our yoked shuttlebox paradigm based on ES and IS. Then, mice were immediately euthanized and RNA extracted from brain regions of interest and loaded into NanoString® Mouse Neuroinflammation Panels for compilation of gene expression profiles. Results showed differential regional effects in gene expression and activated pathways involved in inflammatory-related signaling following ES and IS, and these differences were altered depending on amygdalar excitation or inhibition. These findings demonstrate that the stress-induced immune response, or “parainflammation”, is affected by stressor controllability and that BLA influences regional parainflammation to ES or IS in HPC and mPFC. The study illustrates how stress-induced parainflammation can be regulated at the neurocircuit level and suggests that this approach can be useful for uncovering circuit and immune interactions in mediating differential stress outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02813-x.
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spelling pubmed-102250812023-05-29 Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala Adkins, Austin M. Colby, Emily M. Kim, Woong-Ki Wellman, Laurie L. Sanford, Larry D. J Neuroinflammation Research Increasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can differentially alter inflammatory-related gene expression in brain in a region dependent manner. We have also demonstrated that the basolateral amygdala (BLA) regulates stress- and fear memory-induced alterations in sleep, and that differential sleep and immune responses in the brain to ES and IS appear to be integrated during fear conditioning and then reproduced by fear memory recall. In this study, we investigated the role of BLA in influencing regional inflammatory responses within the hippocampus (HPC) and medial prefrontal cortex (mPFC) by optogenetically stimulating or inhibiting BLA in male C57BL/6 mice during footshock stress in our yoked shuttlebox paradigm based on ES and IS. Then, mice were immediately euthanized and RNA extracted from brain regions of interest and loaded into NanoString® Mouse Neuroinflammation Panels for compilation of gene expression profiles. Results showed differential regional effects in gene expression and activated pathways involved in inflammatory-related signaling following ES and IS, and these differences were altered depending on amygdalar excitation or inhibition. These findings demonstrate that the stress-induced immune response, or “parainflammation”, is affected by stressor controllability and that BLA influences regional parainflammation to ES or IS in HPC and mPFC. The study illustrates how stress-induced parainflammation can be regulated at the neurocircuit level and suggests that this approach can be useful for uncovering circuit and immune interactions in mediating differential stress outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02813-x. BioMed Central 2023-05-27 /pmc/articles/PMC10225081/ /pubmed/37244986 http://dx.doi.org/10.1186/s12974-023-02813-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Adkins, Austin M.
Colby, Emily M.
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title_full Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title_fullStr Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title_full_unstemmed Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title_short Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
title_sort stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225081/
https://www.ncbi.nlm.nih.gov/pubmed/37244986
http://dx.doi.org/10.1186/s12974-023-02813-x
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