Electro-Acupuncture Attenuates Chronic Stress Responses via Up-Regulated Central NPY and GABAA Receptors in Rats

Yu Yang,Jun Zheng,Bei Shi,Reji Babygirija,Weinan Sun,Haijie Yu,Xiaojiao Zheng

doi:10.3389/fnins.2020.629003

Abstract

Stress can increase the release of corticotropin-releasing factor (CRF) in the hypothalamus, resulting in attenuation of gastric motor functions. In contrast, central neuropeptide Y (NPY) can reduce the biological actions of CRF, and in turn weaken stress responses. Although electroacupuncture (EA) at stomach 36 (ST-36) has been shown to have anti-stress effects, its mechanism has not yet been investigated. The effect of EA at ST-36 on the hypothalamus-pituitary-adrenal (HPA) axis and gastrointestinal motility in chronic complicated stress (CCS) conditions have not been studied and the inhibitory mechanism of NPY on CRF through the gamma-aminobutyric acid (GABA)A receptor need to be further investigated. A CCS rat model was set up, EA at ST-36 was applied to the bilateral hind limbs every day prior to the stress loading. Further, a GABAA receptor antagonist was intracerebroventricularly (ICV) injected daily. Central CRF and NPY expression levels were studied, serum corticosterone and NPY concentrations were analyzed, and gastric motor functions were assessed. CCS rats showed significantly elevated CRF expression and corticosterone levels, which resulted in inhibited gastric motor functions. EA at ST-36 significantly increased central NPY mRNA expression and reduced central CRF mRNA expression as well as the plasma corticosterone level, helping to restore gastric motor function. However, ICV administration of the GABAA receptor antagonist significantly abolished these effects. EA at ST-36 upregulates the hypothalamic NPY system. NPY may, through the GABAA receptor, significantly antagonize the overexpressed central CRF and attenuate the HPA axis activities in CCS conditions, exerting influences and helping to restore gastric motor function.

Highlights

The pathogeneses of functional gastrointestinal disorders (FGIDs), such as functional dyspepsia (FD), are highly related to stress in humans (Levy et al, 2006; Talley et al, 2015)
In the chronic complicated stress (CCS) rat model, delayed gastric emptying (GE) and attenuated gastric contraction were observed when rats received different types of stressors for many days, with increased corticotropin-releasing factor (CRF) messenger RNA expression in the paraventricular nucleus (PVN) of the hypothalamus, which resulted in increased hypothalamuspituitary-adrenal (HPA) axis activities (Zheng et al, 2010)
Our present study found that EA at ST36 increased the neuropeptide Y (NPY) messenger RNA (mRNA) expression and decreased CRF mRNA expression at the PVN following CCS, but in the peripheral, EA at ST36 did not change the serum NPY level significantly

Summary

Introduction

The pathogeneses of functional gastrointestinal disorders (FGIDs), such as functional dyspepsia (FD), are highly related to stress in humans (Levy et al, 2006; Talley et al, 2015). Gastrointestinal (GI) dysmotility might develop as a result of the accumulation of repeated or continuous stress in some individuals. Corticotropin-releasing factor (CRF) in the central nervous system plays a significant role in mediation of stress-induced GI dysmotility (Lenz et al, 1988; Tache and Bonaz, 2007). In the chronic complicated stress (CCS) rat model, delayed gastric emptying (GE) and attenuated gastric contraction were observed when rats received different types of stressors for many days, with increased CRF messenger RNA (mRNA) expression in the paraventricular nucleus (PVN) of the hypothalamus, which resulted in increased hypothalamuspituitary-adrenal (HPA) axis activities (Zheng et al, 2010). Peripheral CRF receptor antagonists have been developed, the efficiency of the antagonists to treat stress-induced GI dysmotility remains to be further investigated (Kormos and Gaszner, 2013; Bali et al, 2014)

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Results

Conclusion