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NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype

Anandamide (AEA) is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, being a component of the endocannabinoid signaling system, which supports the maintenance or regaining of neural homeostasis upon internal and external challenges. AEA is thought to play a protective role against the...

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Autores principales: Tevosian, Margaryta, Todorov, Hristo, Lomazzo, Ermelinda, Bindila, Laura, Ueda, Natsuo, Bassetti, Davide, Warm, Davide, Kirischuk, Sergei, Luhmann, Heiko J., Gerber, Susanne, Lutz, Beat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164145/
https://www.ncbi.nlm.nih.gov/pubmed/37149657
http://dx.doi.org/10.1038/s41398-023-02448-9
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author Tevosian, Margaryta
Todorov, Hristo
Lomazzo, Ermelinda
Bindila, Laura
Ueda, Natsuo
Bassetti, Davide
Warm, Davide
Kirischuk, Sergei
Luhmann, Heiko J.
Gerber, Susanne
Lutz, Beat
author_facet Tevosian, Margaryta
Todorov, Hristo
Lomazzo, Ermelinda
Bindila, Laura
Ueda, Natsuo
Bassetti, Davide
Warm, Davide
Kirischuk, Sergei
Luhmann, Heiko J.
Gerber, Susanne
Lutz, Beat
author_sort Tevosian, Margaryta
collection PubMed
description Anandamide (AEA) is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, being a component of the endocannabinoid signaling system, which supports the maintenance or regaining of neural homeostasis upon internal and external challenges. AEA is thought to play a protective role against the development of pathological states after prolonged stress exposure, including depression and generalized anxiety disorder. Here, we used the chronic social defeat (CSD) stress as an ethologically valid model of chronic stress in male mice. We characterized a genetically modified mouse line where AEA signaling was reduced by deletion of the gene encoding the AEA synthesizing enzyme N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) specifically in neurons activated at the time of CSD stress. One week after the stress, the phenotype was assessed in behavioral tests and by molecular analyses. We found that NAPE-PLD deficiency in neurons activated during the last three days of CSD stress led to an increased anxiety-like behavior. Investigating the molecular mechanisms underlying this phenotype may suggest three main altered pathways to be affected: (i) desensitization of the negative feedback loop of the hypothalamic-pituitary-adrenal axis, (ii) disinhibition of the amygdala by the prefrontal cortex, and (iii) altered neuroplasticity in the hippocampus and prefrontal cortex.
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spelling pubmed-101641452023-05-08 NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype Tevosian, Margaryta Todorov, Hristo Lomazzo, Ermelinda Bindila, Laura Ueda, Natsuo Bassetti, Davide Warm, Davide Kirischuk, Sergei Luhmann, Heiko J. Gerber, Susanne Lutz, Beat Transl Psychiatry Article Anandamide (AEA) is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, being a component of the endocannabinoid signaling system, which supports the maintenance or regaining of neural homeostasis upon internal and external challenges. AEA is thought to play a protective role against the development of pathological states after prolonged stress exposure, including depression and generalized anxiety disorder. Here, we used the chronic social defeat (CSD) stress as an ethologically valid model of chronic stress in male mice. We characterized a genetically modified mouse line where AEA signaling was reduced by deletion of the gene encoding the AEA synthesizing enzyme N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) specifically in neurons activated at the time of CSD stress. One week after the stress, the phenotype was assessed in behavioral tests and by molecular analyses. We found that NAPE-PLD deficiency in neurons activated during the last three days of CSD stress led to an increased anxiety-like behavior. Investigating the molecular mechanisms underlying this phenotype may suggest three main altered pathways to be affected: (i) desensitization of the negative feedback loop of the hypothalamic-pituitary-adrenal axis, (ii) disinhibition of the amygdala by the prefrontal cortex, and (iii) altered neuroplasticity in the hippocampus and prefrontal cortex. Nature Publishing Group UK 2023-05-06 /pmc/articles/PMC10164145/ /pubmed/37149657 http://dx.doi.org/10.1038/s41398-023-02448-9 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
Tevosian, Margaryta
Todorov, Hristo
Lomazzo, Ermelinda
Bindila, Laura
Ueda, Natsuo
Bassetti, Davide
Warm, Davide
Kirischuk, Sergei
Luhmann, Heiko J.
Gerber, Susanne
Lutz, Beat
NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title_full NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title_fullStr NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title_full_unstemmed NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title_short NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
title_sort nape-pld deletion in stress-traped neurons results in an anxiogenic phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164145/
https://www.ncbi.nlm.nih.gov/pubmed/37149657
http://dx.doi.org/10.1038/s41398-023-02448-9
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