Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

Xiu-Fang Ding,Yuan-Liang Liu,Jian-Xin Diao,Wei-Chao Zhong,Yang Tao,Jia-Xu Chen,Yu-Yao Chen,Qin Fan,Xiao-Hua Zhao,Zhi-Ping Lv

doi:10.1155/2014/605914

Abstract

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

Highlights

Stress response is a risk factor that can develop affective or mental disorders, including anxiety, posttraumatic stress disorder, depression, and other disorders [1] and is characterized by the activation of the Locus coeruleus-norepinephrine (LCNE) system
Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis [12], hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonad (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress [13, 14], while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) or compounds on the mechanisms of locus coeruleus-norepinephrine (LC-NE) systems have been reported
In order to avoid the restraint adaptability of rats, chronic immobilization stress (CIS) protocol made a minor modification according to previous studies [21, 26]

Summary

Introduction

Stress response is a risk factor that can develop affective or mental disorders, including anxiety, posttraumatic stress disorder, depression, and other disorders [1] and is characterized by the activation of the Locus coeruleus-norepinephrine (LCNE) system. The locus coeruleus in brainstem noradrenergic neurons during stress period can supply norepinephrine (NE) across the central nervous system (CNS) to form a LC-NE system and modulate the central stress response. Norepinephrine-synthesizing enzymes including TH and DBH may be a neurochemical mechanism to interpret behavioral depression [6]. Both TH and DBH gene expressions in LC can be induced rapidly after immobilization stress [6, 7]. Either autonomic or emotional stress activates CRF release in the LC region, which in turn

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Conclusion