Abstract

Xiaoyaosan (XYS) decoction has been widely used as a traditional medicine for treating stress and depression-related disorders in China for thousands of years. Aim of the Study. To observe the potential mechanism of XYS decoction's antidepressant-like effect in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors related to synaptic plasticity in the hippocampus rats induced by chronic immobilization stress (CIS). Materials and Methods. Animals were randomly divided into five groups: (1) control group; (2) sham-operated group; (3) CIS group, in which rats were conducted CIS for 21 days; (4) XYS decoction treatment group; (5) 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) positive group, in which the amygdala of CIS rats was unilaterally microinjected with a competitive glutamate receptor antagonist, CNQX. After CIS for 21 days, the open field test (OPT) and elevated plus-maze test (EPM) were measured, the ultrastructure of hippocampus CA1 subregion was observed by the electron microscopy; both the GluR1 and GluR2 mRNA level of AMPA receptor subunits in hippocampus CA1 subregion were detected by real-time qPCR. Results. Rats subjected to CIS exhibited increases in time in central zone and decreases in total distance traveled in the OPT. In the EPM, they also showed decreases in center zone time and entries, open arm time and entries, and an increase in close arm time. Ultrastructural damage in the hippocampus CA1 was also observed. XYS decoction and CNQX showed significant improvement behavioral changes and the ultrastructural damage of the hippocampus CA1; XYS decoction also reversed CIS-induced decreases in GluR2 mRNA and increases in GluR1 mRNA in the hippocampus CA1 as well as CNQX. Conclusions. XYS decoction may effectively produce an antidepressant-like effect, which appears to be involved AMPA receptors related synaptic plasticity of hippocampus.

Highlights

  • There is abundant evidence demonstrating that chronic stress can cause hippocampal damage, such as dendritic remodeling, synaptic plasticity, dendrites retracting, decreased neurogenesis, and apoptosis [1]

  • The decreased total distance traveled was effectively reversed by the treatment with CNQX or XYS decoction (P < 0.01); the time in central zone decreased after treatment, but no statistical difference was shown (P > 0.05)

  • Several variables can be measured in the open field; for instance, time spent in the center is considered to indicate emotional reactivity, and total distance traveled is thought to indicate locomotor and exploratory activity [17, 18]

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Summary

Introduction

There is abundant evidence demonstrating that chronic stress can cause hippocampal damage, such as dendritic remodeling, synaptic plasticity, dendrites retracting, decreased neurogenesis, and apoptosis [1]. Stress induced anxiety and depression involve multiple areas of the brain, such as amygdale and the prefrontal cortex. Both the hippocampus and the amygdala are important aspects of the limbic system which plays a dominant role in stress response. The amygdala projects to several hippocampal regions (including the CA1 area) [3, 4]. Functionally, both of them control the systems involved in stress. Both of them control the systems involved in stress It seems that they have different actions during stress response. There were findings about enlarged amygdala volume and reduced hippocampus volume in young women

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