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

Han F, Yan S, Shi Y - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.

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.

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TEM images of the hippocampus in the SPS rats.TEM images of the hippocampus. A: Normal control hippocampal neuron, displaying abundant organelles such as mitochondria, endoplasmic reticulum, and ribosomes. The nucleus is large and round, density of chromatin is uniform, and nucleolus is clear. B: Chromatin margination, in the form of crescent formation in nucleus (arrow), is shown. C: The cells showed some typical structural changes indicative of apoptosis, such as chromatin dissolution and, nuclear envelope breakdown (star). Scale bar = 200 nm (A). Scale bar = 300 nm (B and C).
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pone-0069340-g002: TEM images of the hippocampus in the SPS rats.TEM images of the hippocampus. A: Normal control hippocampal neuron, displaying abundant organelles such as mitochondria, endoplasmic reticulum, and ribosomes. The nucleus is large and round, density of chromatin is uniform, and nucleolus is clear. B: Chromatin margination, in the form of crescent formation in nucleus (arrow), is shown. C: The cells showed some typical structural changes indicative of apoptosis, such as chromatin dissolution and, nuclear envelope breakdown (star). Scale bar = 200 nm (A). Scale bar = 300 nm (B and C).

Mentions: As shown in Fig. 2, the hippocampal cells in the control rats exhibited normal morphology (Fig. 2A). Some cells in the hippocampus of SPS rats (Figs. 2B, 2C) exhibited changes characteristic of apoptosis, including chromatin condensation, appearance of chromatin crescents (shown with arrow), nucleus fragmentation (shown with star) and nucleolus disappearance.


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

Han F, Yan S, Shi Y - PLoS ONE (2013)

TEM images of the hippocampus in the SPS rats.TEM images of the hippocampus. A: Normal control hippocampal neuron, displaying abundant organelles such as mitochondria, endoplasmic reticulum, and ribosomes. The nucleus is large and round, density of chromatin is uniform, and nucleolus is clear. B: Chromatin margination, in the form of crescent formation in nucleus (arrow), is shown. C: The cells showed some typical structural changes indicative of apoptosis, such as chromatin dissolution and, nuclear envelope breakdown (star). Scale bar = 200 nm (A). Scale bar = 300 nm (B and C).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3716639&req=5

pone-0069340-g002: TEM images of the hippocampus in the SPS rats.TEM images of the hippocampus. A: Normal control hippocampal neuron, displaying abundant organelles such as mitochondria, endoplasmic reticulum, and ribosomes. The nucleus is large and round, density of chromatin is uniform, and nucleolus is clear. B: Chromatin margination, in the form of crescent formation in nucleus (arrow), is shown. C: The cells showed some typical structural changes indicative of apoptosis, such as chromatin dissolution and, nuclear envelope breakdown (star). Scale bar = 200 nm (A). Scale bar = 300 nm (B and C).
Mentions: As shown in Fig. 2, the hippocampal cells in the control rats exhibited normal morphology (Fig. 2A). Some cells in the hippocampus of SPS rats (Figs. 2B, 2C) exhibited changes characteristic of apoptosis, including chromatin condensation, appearance of chromatin crescents (shown with arrow), nucleus fragmentation (shown with star) and nucleolus disappearance.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.

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.

Show MeSH
Related in: MedlinePlus