Authors:	Tevosian, Margaryta Todorov, Hristo Lomazzo, Ermelinda Bindila, Laura Ueda, Natsuo Basetti, Davide Warm, Davide Kirischuk, Sergei Luhmann, Heiko J. Gerber, Susanne Lutz, Beat
Title:	NAPE-PLD deletion in stress-TRAPed neurons results in an anxiogenic phenotype
Online publication date:	26-Jan-2024
Year of first publication:	2023
Language:	english
Abstract:	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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9975
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Translational Psychiatry 13
Pages or article number:	152
Publisher:	Nature Publishing Group
Publisher place:	London
Issue date:	2023
ISSN:	2158-3188
Publisher DOI:	10.1038/s41398-023-02448-9
Appears in collections:	DFG-491381577-G