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

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-Fas lpr ). 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.

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions

“…These data further extend CLA anti-neuroinflammatory actions, demonstrated in cultured astrocytes [186] and in vivo, where it has been shown that chronic dietary CLA intake reduces prostaglandin E2, decreases the activity of the endocannabinoid system, and inhibits angiogenesis in the mammalian brain [187][188][189]. In a murine model of autoimmune disease, it has been shown that the protective effect of CLA on age-dependent biochemical signs of neurodegeneration and depression are associated with the activation of Nrf2-mediated cytoprotective defences [190,191]. In addition, CLA protects against the disease-associated decline of synaptogenesis [190].…”

Systematic impacts of chronic unpredictable mild stress on metabolomics in rats

“…Additionally, nuclear erythroid-related factor 2 (Nrf2) was involved in metabolic homeostasis and inflammation and has become a promising target for the prevention or treatment of depressive disorders. As earlier researches showed that fish oil and conjugated linoleic acid can induce Nrf2 upregulation, their protective ability has been evaluated in a rat model of depression 28,29 . The discovery that the levels of linoleic acid, palmitic acid, stearic acid, oleamide, and palmitoleic www.nature.com/scientificreports www.nature.com/scientificreports/ acid were significantly altered in the CUMS group compared to the control rats may help to understand the molecular mechanisms associated with inflammation and oxidative stress that underlie depression.…”

Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

“…Oxidative stress is an etiologic factor in depressive/neurodegenerative disorders that it is often accompanied by deregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, a key antioxidant mechanism indicated as a promising target for treatment of depression [ 14 ]. As a pivotal transcription factor, Nrf2 was involved in the regulation of the antioxidant response in the brain.…”