Brain Behav. , 2020., Jun;10(6):e01626. doi: 10.1002/brb3.1626.

Antidepressant-like Effect of Flaxseed in Rats Exposed to Chronic Unpredictable Stress

Abstract

Introduction: Depression is a serious mental illness. However, a significant proportion of patients with depression fail to achieve remission with antidepressant therapies. This study was conducted to explore the antidepressant-like effect of flaxseed oil and flour in an animal model with depression-like behaviors induced by chronic unpredictable stress (CUS). Methods: Rats were randomly divided into five groups: normal control (Sham-Sham), CUS plus saline (S-SN), CUS plus escitalopram (S-Esc), CUS plus flaxseeds oil (S-FO), and CUS plus flaxseed flour (S-FF). Behaviors were tested using sucrose preference test and forced swimming test. The serum BDNF concentration, hippocampal BDNF mRNA, and protein expression were measured by enzyme-linked immunosorbent assay, real-time PCR, and Western blot, respectively. Results: The sucrose preference rate was significantly higher in S-FO and S-FF rats than in S-SN and S-Esc rats (p < .01), and lower in S-Esc rats than in Sham-Sham rats (p < .01). The immobility time was significantly shorter in S-FO and S-FF rats than in S-SN rats (p < .01), and shorter in S-Esc rats than in S-SN rats (p < .01). Plasma BDNF concentrations were significantly lower in S-FO, S-FF, and S-Esc rats than in Sham-Sham rats (p < .01); BDNF was lower in S-FO, S-FF, and S-SN rats than in S-Esc rats. The hippocampal BDNF protein expression was significantly higher in S-Esc rats than in S-SN rats (p < .05). The hippocampal BDNF mRNA expression was significantly higher in S-Esc rats than in S-SN rats (p < .01). The BDNF gene expression in plasma and the hippocampus negatively correlated with the immobility time (p < .05), but BDNF gene expression in the hippocampus positively correlated with the sucrose preference rate (p < .05). Conclusion: Flaxseed oil and flaxseed flour exert antidepressant-like effect in rats exposed to chronic stress. Flaxseed may have a therapeutic effect on depression.

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Key Points

n‐3 PUFAs may improve LPS‐induced depression‐like behaviors in rodents through regulating BDNF functions. In addition, flaxseed has many polyphenolic compounds such as phenolic acids, flavonoids, and lignans.  In this study, the antidepressant‐like effects of chronic administration of flaxseed oil (oil extracted from flaxseed) and flour (by‐product of flaxseed degreasing) were analyzed in animal models of depression established by chronic unpredictable stress (CUS, a well‐verified depressogenic stressor). Escitalopram, a selective serotonin reuptake inhibitor (SSRI), was used as a positive control of antidepressant. The BDNF expression in the hippocampus was measured to further understand the possible mechanism of flaxseed oil and flour. Unpredictable chronic mild stress mimics the environmental stressors that people might experience in daily life.  The antidepressant effects of flaxseed oil in the SPT were better than with flaxseed flour, even better than the standard antidepressant escitalopram. The different observation could be explained that SSRIs do not principally address anhedonia, which is associated with strong deficits in the dopamine system. Flaxseed oil and flaxseed flour exert antidepressant-like effect in rats exposed to chronic stress. Flaxseed may have a therapeutic effect on depression.