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ABSTRACT: INTRODUCTION: Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS). The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter. METHODS: In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM). Levels of Cytochrome c (Cyt-C) was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM). The change of thiamine monophosphatase (TMP) levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM. RESULTS: Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS. CONCLUSIONS: The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated with PTSD.
BMC Psychiatry 11/2012; 12(1):211. · 2.55 Impact Factor
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ABSTRACT: Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Mental disorder appears after the traumatic stress incident and affects the movement of the eye muscle dominated by the oculomotor nucleus, an important nuclear group of the brainstem. It has been reported that dysfunction of the neurotransmitter 5-hydroxytryptamine (5-HT) can lead to the instability of the internal environment in response to stress and plays an important role in the pathology of PTSD and that the 5-HT1A receptor (5-HT1AR) is critically involved in regulating mood and anxiety levels. In this study, the 5-HT1AR expression in the oculomotor nucleus was examined in rats with single-prolonged stress (SPS), a well established post-traumatic stress disorder animal model. Our results show that the expression of 5-HT1AR in the oculomotor nucleus neurons gradually increased 1, 4, and 7 days after exposure to SPS in comparison to the normal control group, measured by immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). The expression of 5-HT1AR reached its peak 7 days after the SPS exposure and then decreased 14 days after. There is also a change in the ultrastructure in the oculomotor nucleus neuron upon SPS treatment which was observed by transmission electron microscopy. These results suggest that SPS can induce a change of the 5-HT1AR expression in the oculomotor nucleus, which may be one of the molecular mechanisms that lead to PTSD.
Journal of Molecular Neuroscience 08/2012; · 2.50 Impact Factor
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ABSTRACT: The extracellular signal-regulated kinase (ERK) signaling transduction pathway has been implicated in multiple physiological processes. It is not clear whether the ERK1/2 pathway participates in post-traumatic stress disorder (PTSD). The aim of this study was to provide novel insights into the mechanisms of how the amygdala participates in PTSD by investigating changes in the ERK1/2 pathway induced by single prolonged stress (SPS). The level of phosphorylated ERK1/2 (pERK1/2) protein was defined in a single-prolonged stress (SPS) animal model of post-traumatic stress disorder. A total of 100 male Wistar rats were randomly divided into a normal control group and SPS groups of 0, 30, 60 and 120 min. pERK1/2 distribution in the amygdala neurons was observed using immune electron microscopy. The expression of pERK1/2 was examined by immunohistochemistry and Western blotting. The pERK protein was located in some cell organelles, such as the mitochondria and neuraxon. Quantitatively, the expression of pERK protein level was significantly increased in the SPS rats. The results suggest that the ERK signal transduction pathway may play a crucial role in the pathology of PTSD.
Molecular Medicine Reports 05/2011; 4(3):445-9. · 0.42 Impact Factor
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ABSTRACT: The purpose of this study was to provide a novel insight into the mechanism of how amygdala might participate in PTSD by investigating the changes of cytochrome c oxidase (COX), caspase-9, and caspase-3 in the amygdala of single-prolonged stress (SPS) rats. A total of 80 healthy, male Wistar rats were selected for this study. The models of post-traumatic stress disorder (PTSD) were created by SPS, which is an established animal model for PTSD. The change of COX was detected by light microscope and transmission electron microscopy (TEM). The expression of caspase-9 and caspase-3 in the basolateral amygdala was examined by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). SPS exposure resulted in a significant change of COX in the SPS model groups compared with the normal control group. Evaluation by enzymohistochemistry indicated translocation of COX from mitochondria to cytoplasm. The expression of both caspase-9 and caspase-3 significantly increased 1 day after SPS stimulation, then gradually increased and peaked at SPS 7d. This findings suggest changes of COX, caspase-9, and caspase-3 in the amygdala of SPS rats, which may play important roles in the pathogenesis of PTSD.
Cellular and Molecular Neurobiology 01/2011; 31(1):37-43. · 1.97 Impact Factor
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ABSTRACT: Single-prolonged stress (SPS) is an established animal model for post-traumatic stress disorder (PTSD). The calcium (Ca2+)-calmodulin (CaM)-CaM kinase (K)IIalpha signal passage plays an important role in the plasticity of central nervous, learning and memory, mind and behavior and other types of cognitive activities. The amygdala is known to play an important role in fear, rage and emotional memory. In this study, we investigated changes in Ca2+-CaM-CaMKIIalpha in the basolateral amygdala of rats after SPS which may reveal part of the pathogenesis of PTSD. The intracellular free calcium level in the basolateral amygdala was examined by fluorescence spectrophotometry. CaM and CaMKIIalpha expression in basolateral amygdala was examined using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. The intracellular free calcium level in the basolateral amygdala was increased when compared to that in the control group 1 day after SPS exposure (P<0.05). CaM expression significantly increased, and CaMKIIalpha expression significantly decreased (P<0.05) in the basolateral amygdala after SPS. These findings suggest dysfunction of Ca2+-CaM-CaMKIIalpha in the basolateral amygdala of SPS rats, which may play important roles in the pathogenesis of PTSD rats.
International Journal of Molecular Medicine 12/2009; 24(6):795-9. · 1.98 Impact Factor
