Restraint-Induced Expression of Endoplasmic Reticulum Stress-Related Genes in the Mouse Brain

Abstract

Depression is a significant public health concern but its pathology remains unclear. Previously, increases in an endoplasmic reticulum (ER) stress-related protein were reported in the temporal cortex of subjects with major depressive disorder who had died by suicide. This finding suggests an association between depression and ER stress. The present study was designed to investigate whether acute stress could affect the ER stress response. Mice were immobilized for a period of 6 hr and then expression of ER stress response-related genes was measured by real-time PCR. We also used enzyme-linked immunosorbent assay for concomitant measurement of the plasma corticosterone levels in the mice. The effect of corticosterone on ER stress proteins was further investigated by treating mice with corticosterone for 2 weeks and then measuring ER protein expression by Western blotting. After a 6 hr restraint stress, mRNA levels of ER stress-related genes, such as the 78-kilodalton glucose regulated protein (GRP78), the 94-kilodalton glucose regulated protein (GRP94), and calreticulin, were increased in the cortex, hippocampus, and striatum of mouse brain. Blood plasma corticosterone level was also increased. In the corticosterone-treated mouse model, the expression of GRP78 and GRP94 was significantly increased in the hippocampus. These results suggest that acute stress may affect ER function and that ER stress may be involved in the pathogenesis of restraint stress, including the development of depression

Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress

“…6) Recently, we found that 6 h restraint stress increased in the expression of endoplasmic reticulum stress-related genes in the mouse brain and plasma corticosterone levels. 7) These findings indicate a possibility of a relationship among exogenous stress, endoplasmic reticulum stress, and corticosterone.…”

“…6) Recently, we have reported that restraint stress increases in the expression of endoplasmic reticulum stress-related genes in the mouse brain. 7) These findings indicate that endoplasmic reticulum stress may have some roles in the pathogenesis of depression.…”

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

“…Enhanced expression and activation of ER stress and UPR markers have been observed in animal models of depression based on chronic stress procedures in adults [ 27 – 29 ] and in different acute stress models [ 53 , 54 ]. Moreover, the infusion of tunicamycin, an activator of the UPR, into the hippocampus produces a depressive-like phenotype in rats [ 55 ].…”

Cognitive Improvement by Vorinostat through Modulation of Endoplasmic Reticulum Stress in a Corticosterone-Induced Chronic Stress Model in Mice

“…C/EBP homologous protein (CHOP), a transcriptional regulator induced by ER stress, is involved in directing the overwhelmed UPR toward activation of pathways linked to induction of cell death. It can also promote calcium release into the cytoplasm, activating apoptosis. ,, Bax inhibitor-1 (BI-1), an antiapoptotic protein residing in ER membrane is also linked to cell death pathways activated by ER stress …”

“…It can also promote calcium release into the cytoplasm, activating apoptosis. 10,13,14 Bax inhibitor-1 (BI-1), an antiapoptotic protein residing in ER membrane is also linked to cell death pathways activated by ER stress. 15 It has been proposed that histone deacetylase (HDAC) inhibitors might be promising treatments not only for MDD 16 but also for disorders associated with memory impairment.…”