Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder

Wen, Yu; Li, Bin; Han, Fang; Wang, Enhua; Shi, Yonghui

doi:10.3892/mmr.2012.1022

Cited by 26 publications

(14 citation statements)

References 29 publications

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“…Given in our previous studies, our research teammate Wen et al [51] have proved that there were abnormal expression of Ca 2+ -CaM-CaMKIIα pathway in the mPFC neurons, and dysfunction of cytosolic Ca2+ concentration was taken as one of inducement of ER stress, we deduced that ER stress would be induced by dysfunction of Ca 2+ -CaM-CaMKIIα pathway in the mPFC neurons. And at the same time, our teammate Yana et al have found that there were expression changes of bcl-2 and bax in the mPFC neurons of SPS-model rats [10]; Zhao et al [52] also have examined the apoptosis morphological changes by transmission electron microscopy (TEM) and demonstrated the existence of apoptosis in the mPFC neurons of rats after SPS.…”

Section: Discussionmentioning

confidence: 92%

Single Prolonged Stress induces ATF6 alpha-dependent Endoplasmic reticulum stress and the apoptotic process in medial Frontal Cortex neurons

Wen

Xiao

et al. 2014

BMC Neurosci

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BackgroundIn our previous researches, we have found that apoptosis was induced in the medial prefrontal cortex (mPFC) 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) induced apoptosis in the mPFC of PTSD rats by examining the expression levels of ATF6 alpha (ATF6α), two important downstream molecular chaperones of ATF6α in the ER stress: Glucose-regulated protein (GRP) 78 and ERP57, and apoptotic factors caspase 12, caspase 9, and caspase 3.ResultsOur results of Morris Water Maze (MWM) test showed that after SPS exposure, a striking increase of the escape latency was observed in SPS rats at day 1 through day 6, and SPS rats had much less time spent in target quadrant compared to control rats ( P < 0.01). And From immunofluorescence assays, we found that there was a gradual increase on the protein expression of ATF6α in response to SPS, which indicated ATF6α was activated by SPS. And additionally, immunohistochemistry assays, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that the immunoreactivity, protein and mRNA expression of GRP78 and ERP57 increased on 1, 4 days, and peaked on 7 days after SPS exposure, which revealed that SPS triggered inductions of GRP78 and ERP57 in the mPFC neurons. Moreover, RT-PCR assays demonstrated that there were up-regulations in the transcripts levels of caspase 12, caspase 9, and caspase 3 in response to SPS, which were according with the proteins changes of these apoptotic factors and indicated that ER stress and the activation of caspases contributed to SPS.ConclusionCurrent data in this study highlight that SPS induced ATF6α-dependent Endoplasmic reticulum stress and ER-related apoptosis in the mPFC neurons, which indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.

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Section: Discussionmentioning

confidence: 92%

Single Prolonged Stress induces ATF6 alpha-dependent Endoplasmic reticulum stress and the apoptotic process in medial Frontal Cortex neurons

Wen

Xiao

et al. 2014

BMC Neurosci

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“…A recent study by Ji et al has reported an increase in the expressions of L-type calcium channels and alteration in calcium homeostasis in the hippocampus region in PTSD [21]. Moreover, the intracellular calcium level was also found to be increased in the amygdala and medial prefrontal cortex region in response to traumatic stress [19,44]. Therefore, it may be proposed that electric foot-shock trauma may potentiate the activity of L-type calcium channels in the stress-responsive brain regions to disrupt the calcium homeostasis, which in turn may be responsible for observed behavioral alterations in mice, reminiscent of PTSD symptoms.…”

Section: Discussionmentioning

confidence: 99%

Investigating the role of nisoldipine in foot‐shock‐induced post‐traumatic stress disorder in mice

Verma

Bali

Singh

et al. 2016

Fundamemntal Clinical Pharma

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This study was designed to investigate the effectiveness of nisoldipine, an L-type voltage-sensitive calcium channel blocker, to ameliorate anxiety and fear response in a mouse model of post-traumatic stress disorder (PTSD). Acute trauma was induced in Swiss albino mice in a 2-day electric foot-shock paradigm consisting of 15 intermittent foot-shocks of 0.8 mA intensity, 10-s duration and 10-s intershock interval, during 5 min, followed by 3 weekly situational reminders, that is, once per week in the same context on three successive weeks. PTSD-induced behavioral changes were assessed using actophotometer, open-field, social interaction test, and freezing behavior. Biochemically, the serum corticosterone levels were estimated. Electric foot-shock and situational reminders produced behavioral alterations and decreased corticosterone levels, assessed on the 21st day following the traumatic event. Administration of sertraline (Ser 15 mg/kg), a selective serotonin reuptake inhibitor (SSRI) and nisoldipine (20 and 40 mg/kg), significantly attenuated the foot-shock-trauma-induced behavioral changes along with normalization of the corticosterone levels. It may be concluded that nisoldipine produces beneficial effects in re-establishing behavioral alterations, which may be due to normalization of reduced corticosterone levels in PTSD in mice.

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“…Numerous studies have revealed that the amygdala, hippocampus and medial prefrontal cortex (mPFC) are closely associated with the occurrence of PTSD ( 4 ). The mPFC is a higher-order structure that controls the stress and fear responses of the amygdala and the hippocampus ( 5 ). Computed tomography and functional magnetic resonance imaging have confirmed that the mPFC in the brains of patients with PTSD is significantly smaller than that of healthy individuals, and that their emotional adjustment function is weakened ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Changes in integrin αv, vinculin and connexin43 in the medial prefrontal cortex in rats under single-prolonged stress

Han

Shi

2014

Molecular Medicine Reports

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Post-traumatic stress disorder (PTSD) is a stress-accociated mental disorder that occurs as a result of exposure to a traumatic event, with characteristic symptoms, including intrusive memories, hyperarousal and avoidance. The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment, particularly introspection, inhibition of the amygdala and emotional memory. Previous structural neuroimaging studies have revealed that the mPFC of PTSD patients was significantly smaller when compared with that of controls and their emotional adjustment function was weakened. However, the mechanisms that cause such atrophy remain to be elucidated. The aim of the present study was to elucidate the possible mechanisms involved in apoptosis induced by single-prolonged stress (SPS) in the mPFC of PTSD rats. SPS is an animal model reflective of PTSD. Of the proposed animal models of PTSD, SPS is one that has been shown to be reliably reproducible in patients with PTSD. Wistar rats were sacrificed at 1, 4, 7 and 14 days after exposure to SPS. Apoptotic cells were assessed using electron microscopy and the TUNEL method. Expression of integrin αv, vinculin and connexin43 were detected using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction. The present results demonstrated that apoptotic cells significantly increased in the mPFC of SPS rats, accompanied with changes in expression of integrin αv, vinculin and connexin43. The present results indicated that SPS-induced apoptosis in the mPFC of PTSD rats and the mitochondrial pathway were involved in the process of SPS-induced apoptosis.

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Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder

Cited by 26 publications

References 29 publications

Single Prolonged Stress induces ATF6 alpha-dependent Endoplasmic reticulum stress and the apoptotic process in medial Frontal Cortex neurons

Single Prolonged Stress induces ATF6 alpha-dependent Endoplasmic reticulum stress and the apoptotic process in medial Frontal Cortex neurons

Investigating the role of nisoldipine in foot‐shock‐induced post‐traumatic stress disorder in mice

Changes in integrin αv, vinculin and connexin43 in the medial prefrontal cortex in rats under single-prolonged stress

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