Daidzein Alleviates Hypothalamic-Pituitary-Adrenal Axis Hyperactivity, Ameliorates Depression-Like Behavior, and Partly Rectifies Circulating Cytokine Imbalance in Two Rodent Models of Depression.

Long Chen,Yunpeng Zhang,Pengfei Gao,Bing Li,Hequan Zhong,Cuiting Wang,Xiaokun Wang

doi:10.3389/fnbeh.2021.671864

Long Chen, Yunpeng Zhang + Show 5 more

Open Access

https://doi.org/10.3389/fnbeh.2021.671864

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Abstract

Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.

Highlights

Mood and anxiety disorders have become one of the leading causes of disabilities and burdens in modern society with respect to direct medical costs and productivity loss (Vollbehr et al, 2018)
In the open field test (OFT), the total distance covered by the helpless rats significantly decreased (Figure 2D; F = 29.375; p < 0.001 vs. normal), whereas DD significantly reversed this depression-like behavior by increasing the total distance (p < 0.01 vs. model)
Since less than one-third of patients with major depression attain remission with an antidepressant trial, which indicates that there may be other mechanisms involved in the occurrence of anxiety and depression

Summary

Introduction

Mood and anxiety disorders have become one of the leading causes of disabilities and burdens in modern society with respect to direct medical costs and productivity loss (Vollbehr et al, 2018). As a major mental disease, depression affects approximately 12%–17% of the global population, at some point in their lives (Lopez-Torres, 2019). The pathogenesis of anxiety disorders is unclear. There is a close relationship between serotonin and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants, their therapeutic effects do not emerge until several weeks later (Harmer and Cowen, 2013). Less than one-third of patients with major depression attain remission with an initial antidepressant trial, which means that there may be other pathogeneses of anxiety disorder. It is necessary to further explore the pathogenesis of anxiety and identify new antianxiety drugs

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