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Front. Neurosci. | doi: 10.3389/fnins.2018.00974

Anxiolytic- and antidepressant-like effects of fish oil-enriched diet in brain-derived neurotrophic factor deficient mice

Juliane Zemdegs1, Eliane Ribeiro2, Cindy Grossmann1, Quentin Rainer3, Delphine Rousseau4, Alain Grynberg5 and  Bruno P. Guiard1, 6*
  • 1UMR5169 Centre de Recherches sur la Cognition Animale (CRCA), France
  • 2University of São Paulo, Brazil
  • 3Faculté de Pharmacie, Université Paris-Sud, France
  • 4Institut National de la Recherche Agronomique, Université Paris-Saclay, France
  • 5INRA Centre Jouy-en-Josas, France
  • 6Université de Toulouse, France

Despite significant advances in the understanding of the therapeutic activity of antidepressant drugs, treatment-resistant depression is a public health issue prompting research to identify new therapeutic strategies. Evidence strongly suggests that nutrition might exert a significant impact on the onset, the duration and the severity of major depression. Accordingly, preclinical and clinical investigations demonstrated the beneficial effects of omega-3 fatty acids in anxiety and mood disorders. Although the neurobiological substrates of its action remain poorly documented, basic research has shown that omega-3 increases brain-derived neurotrophic factor (BDNF) levels in brain regions associated with depression, as antidepressant drugs do. In contrast, low BDNF levels and hippocampal atrophy were observed in animal models of depression. In this context, the present study compared the effects of long-lasting fish oil-enriched diet, an important source of omega-3 fatty acids, between heterozygous BDNF+/- mice and their wild-type littermates. Our results demonstrated lower activation of Erk in BDNF+/- mice whereas this deficit was rescued by fish oil-enriched diet. In parallel, BDNF+/- mice displayed elevated hippocampal extracellular 5-HT levels in relation with a local decreased serotonin transporter protein level. Fish oil-enriched diet restored normal serotonergic tone by increasing the protein levels of serotonin transporter. At the cellular level, fish oil-enriched diet increased the pool of immature neurons in the dentate gyrus of BDNF+/- mice and the latter observations coincide with its ability to promote anxiolytic- and antidepressant-like response in these mutants. Collectively, our results demonstrate that the beneficial effects of long-term exposure to fish oil-enriched diet in behavioral paradigms known to recapitulate diverse abnormalities related to the depressive state specifically in mice with a partial loss of BDNF. These findings contrast with the mechanism of action of currently available antidepressant drugs for which the full manifestation of their therapeutic activity depends on the enhancement of serotoninergic and BDNF signalling. Further studies are warranted to determine whether fish oil supplementation could be used as an add-on strategy to conventional pharmacological interventions in treatment-resistant patients and relevant animal models.

Keywords: BDNF, Serotonin, Fish oil (n-3) fatty acids, neurobehavior, antidepressant, anxiolytic

Received: 28 Sep 2018; Accepted: 05 Dec 2018.

Edited by:

Nasser Haddjeri, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Eliyahu Dremencov, Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Slovakia
Amandine Gautier-Stein, INRA Centre Auvergne Rhône Alpes, France  

Copyright: © 2018 Zemdegs, Ribeiro, Grossmann, Rainer, Rousseau, Grynberg and Guiard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Bruno P. Guiard, Université de Toulouse, Toulouse, France,