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

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 inducer, their protective ability was 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 - were preliminarily evaluated in frontal cortex of 8-weeks (Young) and in 22-weeks old animals (Old), which were used as model of depression. These markers were measured in Old mice at the end of a 5-week pre-treatment with FO or CLA (728 or 650 mg kg-1, respectively). Old mice exhibited disrupted Redox homeostasis, compensatory Nrf2 hyperactivation, lower Docosaheaxaenoic acid (DHA), lower BDNF and synaptic function proteins compared to Young mice. FO and CLA treatment relieved 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.