Investigation of the effects of antidepressant treatment on hippocampus and hypothalamus endoplasmic reticulum stress in chronic mild stress induced depression in rats

Abstract

INTRODUCTION: This study aimed to examine the role of endoplasmic reticulum (ER) stress in the pathophysiology of depression in female rats exposed to the chronic mild stress model. METHODS: Chronic mild stress model was constituted in 48 female adult rats were and divided into 4 groups as control, depression, depression+1 mg/kg sertraline, and depression+10 mg/kg sertraline. Subcutaneous drug infusions were performed for 14 days using osmotic minipumps. Expression levels of genes in ER stress pathway were evalulated in hypothalamus and hippocampus tissues of rats. RESULTS: It was found that ATF4 gene expression increased in depression in the hippocampus and decreased with treatment. Hippocampal GRP78 gene expression was downregulated after treatment. Hypothalamic and hippocampal CALR gene expression decreased with treatment, hypothalamic HSP47 gene expression decreased in both treatment groups. Hypothalamic and hippocampal XPB1 gene expression decreased with treatment, hippocampal XPB1 gene expression was further downregulated in the depression +10 mg/kg sertraline group compared to the depression+1 mg/kg sertraline group. DISCUSSION AND CONCLUSION: These findings show that the ER stress mechanism may have a role in the pathophysiology of depression and that this mechanism can be reversed with treatment. The results of our study have been encouraging for human studies and open the way for new projects to understand and accelerate the antidepressant effect.

Keywords

• major depression
• endoplasmic reticulum
• chronic mild stress model
• sertraline
• gene expression