Ferulic Acid Improves Depressive-Like Behavior in Prenatally-Stressed Offspring Rats via Anti-Inflammatory Activity and HPA Axis.

Xingxing Zheng,Yisong Yue,Junli Zhang,Huanhuan Deng,Yiwei Chen,Yanjun Cao,Ying Cheng,Yingchun Li,Yang Li,Sizhe Xia

doi:10.3390/ijms20030493

Abstract

Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases, and immune dysfunction. Ferulic acid (FA) is a dietary phenolic acid that has pharmacological properties, including potent anti-inflammatory action. We used male, prenatally-stressed offspring rats to investigate the anti-depressive-like effects and possible anti-inflammatory mechanism of FA. We determined the animal behaviors, and the mRNA expression and concentration of inflammatory cytokines, and HPA axis. In addition, we assessed the modulation of hippocampal nuclear factor-κB (NF-κB) activation, neuronal nitric oxide synthase (nNOS) and glucocorticoid receptors (GR) expression via western blotting and immunohistochemistry. Administration of FA (12.5, 25, and 50 mg/kg/day, i.g.) for 28 days markedly increased sucrose intake, and decreased immobility time and total number of crossings, center crossings, rearing, and grooming in the male PS offspring. FA significantly reduced IL-6, IL-1β, and TNF-α concentration and increased IL-10 concentration in male, prenatally-stressed offspring, stimulated by the NF-κB pathway. In addition, FA inhibited interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and increased interleukin-10 (IL-10) mRNA and protein expression. Furthermore, FA markedly decreased the serum adrenocorticotropin (ACTH) and corticosterone concentration by the increase of GR protein expression. Taken together, this study revealed that FA has anti-depressive-like effects in male, prenatally-stressed offspring, partially due to its anti-inflammatory activity and hypothalamic-pituitary-adrenal (HPA) axis.

Highlights

Prenatal stress (PS), which refers to stress during pregnancy, has been reported to exert a wide variety of negative emotional and behavioral effects on both human and animal offspring, including depression, anxiety, attention deficit hyperactivity disorder, and especially learning and memory deficits [1,2,3]
This study sought to determine the effect of Ferulic acid (FA) on inflammatory mediators and depressive-like behaviors in male offspring rats exposed to PS
FA administration attenuated the increase in the pro-inflammatory cytokines, IL-1β, IL-6, tumor necrosis factor-α (TNF-α), and decreased IL-10 and depressive-like behavior in PS offspring rats

Summary

Introduction

Prenatal stress (PS), which refers to stress during pregnancy, has been reported to exert a wide variety of negative emotional and behavioral effects on both human and animal offspring, including depression, anxiety, attention deficit hyperactivity disorder, and especially learning and memory deficits [1,2,3]. Immune cells express receptors for a variety of hormones [6] and glucocorticoids (GCs) can affect the development and function of the immune system [7,8]. It has been reported that PS increases the HPA axis reactivity and circulating levels of the stress hormones GCs, and decreases the glucocorticoids receptor (GR) protein expression [11]. Animal models of depressive disorders have shown an increase in pro-inflammatory markers, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α). Many antidepressants have been shown to suppress NF-κB activation and pro-inflammatory transcription [15,16,17,18]

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Methods

Conclusion