Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine

  1. Antoine Cherix  Is a corresponding author
  2. Thomas Larrieu
  3. Jocelyn Grosse
  4. João Rodrigues
  5. Bruce McEwen
  6. Carla Nasca
  7. Rolf Gruetter
  8. Carmen Sandi  Is a corresponding author
  1. École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
  2. Lausanne University Hospital (CHUV), Switzerland
  3. 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

  1. Antoine Cherix

    Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    For correspondence
    ant.cherix@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4168-8273
  2. Thomas Larrieu

    Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Jocelyn Grosse

    Laboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. João Rodrigues

    Laboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Bruce McEwen

    Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Carla Nasca

    Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Rolf Gruetter

    Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Carmen Sandi

    Laboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    For correspondence
    carmen.sandi@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7713-8321

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).

Reviewing Editor

  1. Harm J Krugers, University of Amsterdam, Netherlands

Version history

  1. Received: July 28, 2019
  2. Accepted: January 7, 2020
  3. Accepted Manuscript published: January 10, 2020 (version 1)
  4. 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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  1. Antoine Cherix
  2. Thomas Larrieu
  3. Jocelyn Grosse
  4. João Rodrigues
  5. Bruce McEwen
  6. Carla Nasca
  7. Rolf Gruetter
  8. Carmen Sandi
(2020)
Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine
eLife 9:e50631.
https://doi.org/10.7554/eLife.50631

Share this article

https://doi.org/10.7554/eLife.50631

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