The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chr...

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Autores principales: Becker, Léa J., Fillinger, Clémentine, Waegaert, Robin, Journée, Sarah H., Hener, Pierre, Ayazgok, Beyza, Humo, Muris, Karatas, Meltem, Thouaye, Maxime, Gaikwad, Mithil, Degiorgis, Laetitia, Santin, Marie des Neiges, Mondino, Mary, Barrot, Michel, Ibrahim, El Chérif, Turecki, Gustavo, Belzeaux, Raoul, Veinante, Pierre, Harsan, Laura A., Hugel, Sylvain, Lutz, Pierre-Eric, Yalcin, Ipek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110607/
https://www.ncbi.nlm.nih.gov/pubmed/37069164
http://dx.doi.org/10.1038/s41467-023-37878-y
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author Becker, Léa J.
Fillinger, Clémentine
Waegaert, Robin
Journée, Sarah H.
Hener, Pierre
Ayazgok, Beyza
Humo, Muris
Karatas, Meltem
Thouaye, Maxime
Gaikwad, Mithil
Degiorgis, Laetitia
Santin, Marie des Neiges
Mondino, Mary
Barrot, Michel
Ibrahim, El Chérif
Turecki, Gustavo
Belzeaux, Raoul
Veinante, Pierre
Harsan, Laura A.
Hugel, Sylvain
Lutz, Pierre-Eric
Yalcin, Ipek
author_facet Becker, Léa J.
Fillinger, Clémentine
Waegaert, Robin
Journée, Sarah H.
Hener, Pierre
Ayazgok, Beyza
Humo, Muris
Karatas, Meltem
Thouaye, Maxime
Gaikwad, Mithil
Degiorgis, Laetitia
Santin, Marie des Neiges
Mondino, Mary
Barrot, Michel
Ibrahim, El Chérif
Turecki, Gustavo
Belzeaux, Raoul
Veinante, Pierre
Harsan, Laura A.
Hugel, Sylvain
Lutz, Pierre-Eric
Yalcin, Ipek
author_sort Becker, Léa J.
collection PubMed
description While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control.
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spelling pubmed-101106072023-04-19 The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice Becker, Léa J. Fillinger, Clémentine Waegaert, Robin Journée, Sarah H. Hener, Pierre Ayazgok, Beyza Humo, Muris Karatas, Meltem Thouaye, Maxime Gaikwad, Mithil Degiorgis, Laetitia Santin, Marie des Neiges Mondino, Mary Barrot, Michel Ibrahim, El Chérif Turecki, Gustavo Belzeaux, Raoul Veinante, Pierre Harsan, Laura A. Hugel, Sylvain Lutz, Pierre-Eric Yalcin, Ipek Nat Commun Article While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control. Nature Publishing Group UK 2023-04-17 /pmc/articles/PMC10110607/ /pubmed/37069164 http://dx.doi.org/10.1038/s41467-023-37878-y 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 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Becker, Léa J.
Fillinger, Clémentine
Waegaert, Robin
Journée, Sarah H.
Hener, Pierre
Ayazgok, Beyza
Humo, Muris
Karatas, Meltem
Thouaye, Maxime
Gaikwad, Mithil
Degiorgis, Laetitia
Santin, Marie des Neiges
Mondino, Mary
Barrot, Michel
Ibrahim, El Chérif
Turecki, Gustavo
Belzeaux, Raoul
Veinante, Pierre
Harsan, Laura A.
Hugel, Sylvain
Lutz, Pierre-Eric
Yalcin, Ipek
The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title_full The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title_fullStr The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title_full_unstemmed The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title_short The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
title_sort basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110607/
https://www.ncbi.nlm.nih.gov/pubmed/37069164
http://dx.doi.org/10.1038/s41467-023-37878-y
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