Dietary Supplementation with Fish Oil or Conjugated Linoleic Acid Relieves Depression Markers in Mice by Modulation of the Nrf2 Pathway

Mol Nutr Food Res. 2019 Nov;63(21):e1900243. doi: 10.1002/mnfr.201900243. Epub 2019 Sep 2.

Abstract

Inflammation and oxidative stress play an important role in the pathogenesis of depressive disorders and nuclear erythroid related factor 2 (Nrf2), a regulator of RedOx homeostasis and inflammation, is a promising target for depression prevention/treatment. As fish oil (FO) and conjugated linoleic acid (CLA) are known Nrf2 inducers, their protective ability is comparatively evaluated in a murine model of depression (MRL/MpJ-Faslpr ). Oxidative stress, fatty acids content, and critical factors reflecting brain functioning-namely brain-derived neurotrophic factor (BDNF), synaptic markers, and cholinergic signaling-are preliminarily evaluated in the frontal cortex of 8-week (Young) and in 22-week old animals (Old), which are used as model of depression. These markers are measured in Old mice at the end of a 5-week pretreatment with FO or CLA (728 or 650 mg kg-1 , respectively). Old mice exhibit disrupted Redox homeostasis, compensatory Nrf2 hyperactivation, lower docosaheaxaenoic acid (DHA), and lower BDNF and synaptic function proteins compared to Young mice. FO and CLA treatment relieves almost all the pathophysiological hallmarks at a level comparable to Young mice. Presented data provide the first evidence for the comparable efficacy of FO or CLA supplementation in preventing depression signs in Old MRL/lpr mice, likely through their ability of improving Nrf2-mediated antioxidant defenses.

Keywords: brain derived neurotrophic factor; brain fatty acid profile; conjugated linoleic acid; depression; fish oil; nuclear erythroid related factor-2.

MeSH terms

  • Aging
  • Animals
  • Antidepressive Agents / pharmacology
  • Autoimmunity / drug effects
  • Biomarkers / metabolism
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Depression / diet therapy*
  • Depression / metabolism
  • Depression / pathology
  • Dietary Supplements
  • Docosahexaenoic Acids / metabolism
  • Fatty Acid Elongases / genetics
  • Fatty Acids / metabolism
  • Fish Oils / pharmacology*
  • Inflammation / diet therapy
  • Linoleic Acids, Conjugated / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred MRL lpr
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Stearoyl-CoA Desaturase / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antidepressive Agents
  • Bdnf protein, mouse
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Fatty Acids
  • Fish Oils
  • Linoleic Acids, Conjugated
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Docosahexaenoic Acids
  • Scd2 protein, mouse
  • Stearoyl-CoA Desaturase
  • Fatty Acid Elongases