Abstract
BackgroundOur previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD) rats. Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS) induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP) 78, caspase-12 and Ca2+/CaM/CaMkinaseIIα (CaMkIIα).MethodsWistar rats were sacrificed at 1, 4 and 7 days after SPS. SPS is a reliable animal model of PTSD. The apoptotic cells in the hippocampus were assessed by TUNEL method and transmission electron microscopy (TEM). Free intracellular Ca2+ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkIIα were determined by RT-PCR.ResultsOur results showed that apoptotic cells were increased in the SPS rats. TEM analysis revealed characteristic morphological changes of apoptosis in these cells. We observed that GRP78 was significantly up-regulated during early PTSD, and then recovered at 7 days after SPS. By RT-PCR, we observed that the change in caspase-12 expression level was similar to that in GRP78. Moreover, the free intracellular Ca2+ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKIIα expression decreased significantly in the hippocampus at 1 day after SPS.ConclusionSPS induced change in the expression levels of GRP78, caspase-12 and Ca2+/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.
Highlights
Post-traumatic stress disorder (PTSD) is an anxiety disorder that may develop following exposure to a death threat or serious injury
In the past several years, our research team examined apoptosis in the smaller hippocampus of rats modeled with post-traumatic stress disorder (PTSD) by using single prolonged stress (SPS) [8], [9], [10], which is a reliable animal model of PTSD based on the timedependent dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis [11], [12]
We mainly focused on three important indicators in the endoplasmic reticulum pathway: Glucose-regulated protein (GRP) 78, Caspase-12 and Ca2+/CaM/Calmodulin-dependent Kinase IIa (CaMKIIa), to examine the SPSinduced apoptosis in the hippocampus involved in endoplasmic reticulum pathway
Summary
Post-traumatic stress disorder (PTSD) is an anxiety disorder that may develop following exposure to a death threat or serious injury. This may cause affected individuals to continuously re-experience the traumatic event [1], [2] and react with intense fear, helplessness or horror for years. Our previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD) rats. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS) induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP) 78, caspase-12 and Ca2+/CaM/CaMkinaseIIa (CaMkIIa)
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