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

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Abstract

Emerging evidence suggests that hierarchical status provides 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.

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Author and article information

Contributors

Antoine Cherix:

ORCID: https://orcid.org/0000-0002-4168-8273

Carmen Sandi:

ORCID: https://orcid.org/0000-0001-7713-8321

Harm J Krugers: Role: Reviewing Editor

Christian Büchel: Role: Senior Editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic, pub): 10 January 2020

Publication date Collection: 2020

Volume: 9

Electronic Location Identifier: e50631

Affiliations

[1 ]deptLaboratory for Functional and Metabolic Imaging (LIFMET) École Polytechnique Fédérale de Lausanne (EPFL) LausanneSwitzerland

[2 ]deptLaboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences Ecole Polytechnique Fédérale de Lausanne LausanneSwitzerland

[3 ]deptHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology The Rockefeller University New YorkUnited States

University of Amsterdam Netherlands

University Medical Center Hamburg-Eppendorf Germany

University of Amsterdam Netherlands

Author notes

[†]

Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV), Site de Cery, Lausanne, Switzerland.

Author information

Antoine Cherix https://orcid.org/0000-0002-4168-8273

Carmen Sandi https://orcid.org/0000-0001-7713-8321

Article

Publisher ID: 50631

DOI: 10.7554/eLife.50631

PMC ID: 6970538

PubMed ID: 31922486

SO-VID: 6e6148a7-275f-4ab2-b2a2-80fa0d2c2882

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

History

Date received : 28 July 2019

Date accepted : 07 January 2020