Single-prolonged stress induces endoplasmic reticulum-dependent apoptosis in the hippocampus in a rat model of post-traumatic stress disorder.

Abstract

BACKGROUND:

Our 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 Ca(2+)/CaM/CaMkinaseIIα (CaMkIIα).

METHODS:

Wistar 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 Ca(2+) 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.

RESULTS:

Our 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 Ca(2+) 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.

CONCLUSION:

SPS induced change in the expression levels of GRP78, caspase-12 and Ca(2+)/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.

• Authors: Fang Han, Shengnan Yan, YuXiu Shi
• Journal: PloS one (PLoS One) Vol. 8 Issue 7 Pg. e69340 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23894451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• GRP78 protein, rat
• Heat-Shock Proteins
• RNA, Messenger
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Caspase 12
• Calcium

Topics

• Animals
• Apoptosis
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (genetics, metabolism)
• Calmodulin (genetics, metabolism)
• Caspase 12 (genetics, metabolism)
• Disease Models, Animal
• Endoplasmic Reticulum (metabolism)
• Heat-Shock Proteins (genetics, metabolism)
• Hippocampus (metabolism, ultrastructure)
• Male
• RNA, Messenger (genetics, metabolism)
• Rats
• Stress Disorders, Post-Traumatic (genetics, metabolism)
• Stress, Physiological