Single-Prolonged Stress Induces Endoplasmic Reticulum - Dependent Apoptosis in the Hippocampus in a Rat Model of Post-Traumatic Stress Disorder

被引：60
作者：
Han, Fang [1 ]
Yan, Shengnan [1 ]
Shi, YuXiu [1 ]
机构：
[1] China Med Univ, Inst Pathol & Pathophysiol, PTSD Lab, Dept Histol & Embryol, Shenyang, Peoples R China
来源：
PLOS ONE | 2013年 / 8卷 / 07期
基金：
中国国家自然科学基金;
关键词：
ER STRESS; CELL-DEATH; PROTEIN; CALCIUM; ACTIVATION; EXPRESSION; CASPASE-12; INDUCTION; RESPONSES; CHAPERONE;
D O I：
10.1371/journal.pone.0069340
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 Ca2+/CaM/CaMkinaseII alpha (CaMkII alpha). 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 Ca2+ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkII alpha 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 Ca2+ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKII alpha expression decreased significantly in the hippocampus at 1 day after SPS. Conclusion: SPS induced change in the expression levels of GRP78, caspase-12 and Ca2+/CaM/CaMkII alpha in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.
引用
收藏
页数：12
相关论文
共 48 条
[1]   Post-traumatic stress disorder and amygdala-hippocampectomy [J].
Adami, P ;
König, P ;
Vetter, Z ;
Hausmann, A ;
Conca, A .
ACTA PSYCHIATRICA SCANDINAVICA, 2006, 113 (04) :360-363
[2]   Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response [J].
Bertolotti, A ;
Zhang, YH ;
Hendershot, LM ;
Harding, HP ;
Ron, D .
NATURE CELL BIOLOGY, 2000, 2 (06) :326-332
[3]   Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus [J].
Del Puerto, H. L. ;
Martins, A. S. ;
Moro, L. ;
Milsted, A. ;
Alves, F. ;
Braz, G. F. ;
Vasconcelos, A. C. .
GENETICS AND MOLECULAR RESEARCH, 2010, 9 (01) :151-161
[4]   Transcriptional program of apoptosis induction following interleukin 2 deprivation: Identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor [J].
Devireddy, LR ;
Green, MR .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (13) :4532-4541
[5]   ETHANOL INHIBITS NMDA-INDUCED INCREASES IN FREE INTRACELLULAR CA-2+ IN DISSOCIATED BRAIN-CELLS [J].
DILDY, JE ;
LESLIE, SW .
BRAIN RESEARCH, 1989, 499 (02) :383-387
[6]   Single-prolonged stress induces apoptosis in the amygdala in a rat model of post-traumatic stress disorder [J].
Ding, Jinlan ;
Han, Fang ;
Shi, Yuxiu .
JOURNAL OF PSYCHIATRIC RESEARCH, 2010, 44 (01) :48-55
[7]   Organelle-specific initiation of cell death pathways [J].
Ferri, KF ;
Kroemer, G .
NATURE CELL BIOLOGY, 2001, 3 (11) :E255-E263
[8]   'Unfolding' pathways in neurodegenerative disease [J].
Forman, MS ;
Lee, VMY ;
Trojanowski, JQ .
TRENDS IN NEUROSCIENCES, 2003, 26 (08) :407-410
[9]  
Hedges Dawson W, 2003, Cogn Behav Neurol, V16, P219, DOI 10.1097/00146965-200312000-00003
[10]  
Hendershot LM, 2004, MT SINAI J MED, V71, P289
12345