Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine
- École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
- Lausanne University Hospital (CHUV), Switzerland
- The Rockefeller University, United States
Abstract
Emerging evidence suggests that hierarchical status provide vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance in depressed patients. We investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically-stressed mice using 1H-magnetic resonance spectroscopy (1H-MRS). High rank, but not low rank, mice, as assessed with the tube test, showed behavioral vulnerability to stress, supporting a higher susceptibility of high social rank mice to develop depressive-like behaviors. High rank mice also showed reduced levels of several energy-related metabolites in the NAc that were counteracted by LAC treatment. Therefore, we reveal a metabolic signature in the NAc for antidepressant-like effects of LAC in vulnerable mice characterized by restoration of stress-induced neuroenergetics alterations and lipid function.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Swiss National Science Foundation (31003A-152614)
- Carmen Sandi
Swiss National Science Foundation (31003A-176206)
- Carmen Sandi
Swiss National Science Foundation - NCCR Synapsy (51NF40-158776)
- Carmen Sandi
Swiss National Science Foundation - NCCR Synapsy (51NF40-185897)
- Carmen Sandi
European Union's Seventh Framework Program for Research (603016)
- Carmen Sandi
EPFL-Jebsen Research Program
- Carmen Sandi
Center for Biomedical Imaging - EPFL
- Rolf Gruetter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Harm J Krugers, University of Amsterdam, Netherlands
Ethics
Animal experimentation: All experiments were performed with the approval of the Cantonal Veterinary Authorities (Vaud, Switzerland) and carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609EEC).
Version history
- Received: July 28, 2019
- Accepted: January 7, 2020
- Accepted Manuscript published: January 10, 2020 (version 1)
- Version of Record published: January 20, 2020 (version 2)
Copyright
© 2020, Cherix et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine
eLife 9:e50631.
https://doi.org/10.7554/eLife.50631
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