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.
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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.
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).
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
