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Monoamine oxidase A (MAOA) can catalyze the degradation of a variety of amine neurotransmitter,including serotonin.The abnormalities of these neurotransmitter are closely associated with many psychiatric disorders.Studies have found that MAOA is polymorphic,with a low activity variant (MAOA-L),and a high activity variant (MAOA-H).In this review,through the studies of early stress on human and animal models,the effects of early stress and MAOA polymorphism on the behavior and emotional loop of individuals are analyzed.Analysis shows that,MAOA-L,versus MAOA-H,is more plastic.In early adverse environment,MAOA-L will increase the risk of adult violence,and in the early of energetically favorable environment will reduce the incidence of violence.Abnormality is more likely to occur in the emotional processing and cognitive function in the neural affective loop of individuals with MAOA-L,which makes them more environmentally susceptible than those with MAOA-H.
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Contactin 5 (CNTN5) belongs to a subgroup of the immunoglobulin superfamily.It is highly expressed in the amygdala and occipital lobe of the human brain as well as in the presynaptic terminal of glutamatergic neurons in the auditory system.In recent years,researchers have used animal experiments to identify the biological functions of CNTN5.They have also investigated the relationship between CNTN5 and menial disorders including autism,Alzheimer's disease,and anorexia nervosa among others.Furthermore,immunofluorescence assays have shown that CNTN5 is expressed in glutamatergic neurons in the hypothalamus.A reduction in the number of glutamatergic neurons can cause the long-term potentiation of synapses.Long-term potentiation is an important mechanism in post-traumatic stress disorder (PTSD).It suggests that mutation of CNTN5 may be one of the mechanisms underlying PTSD.We reviewed the research concerning CNTN5 to identify future research directions.
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Objective To observe changes of apoptosis and Caspase-12 expression in hippocampus of the rat model of posttraumatic stress disorder ( PTSD ) .Methods Single prolonged stress ( SPS ) was used to duplicate a rat model of PTSD.Male Wistar rats were randomly divided into 1, 4, 7 days groups after exposure to SPS and a normal control group.Transmission electron microscopy was used to observe morphologic changes of the hippocampus neurons .The expression of Caspase-12 was detected by immunohistochemistry , Western blotting and RT-PCR.Results After SPS, the hippocampus neurons had characteristic morphologic changes of apoptosis , and the expression of Caspase-12 reached the peak at SPS 4d.Conclusion PTSD activates the ERS-mediated apoptosis in hippocampus via Caspase-12, which may be a pathophysiology base of the atrophy of the hippocampus in PTSD .
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ObjectiveTo observe the changes of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and c-fos in the medial prefrontal cortex (mPFC) of post-traumatic stress disorder (PTSD) rats. Methods Male Wistar rats were randomly divided into control group and PTSD model group. The model group rats were exposed to the single-prolonged stress (SPS) to set up the rat PTSD model. The expression of pERK1/2 was detected using immunohistochemistry and Western blotting, and the expression of c-fos mRNA was detected using reverse transcription-polymerase chain reaction (RT-PCR). Results The result of immunohistochemistry analysis showed that the number of pERK1/2-positive cells of control group and model group were 10.4±2.07 and 48.8±10.08 respectively (P<0.01), and integral optical density were 24.955±3.691 and 110.810±10.643 respectively (P<0.01). And Western blotting showed that relative expression quantities of pERK/β-actin were 0.510±0.052 and 1.109±0.106 respectively (P<0.01). The quantities of c-fos mRNA relative expression of control group and model group were 0.267±0.067 and 1.049±0.131 (P<0.01). Conlusion The levels of pERK1/2 and c-fos increase significantly in mPFC of PTSD model rats. The ERK signal transduction pathway in mPFC might play an important role in the pathogenesis of PTSD.
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ObjectiveTo observe the expressions of Caspase-9,Caspase-3, cytochrome C and their relationships, and investigate apoptotic mechanisms in hippocampus of post-traumatic stress disorder(PTSD) rats. Methods Sixty male Wistar rats were used in the present study. The single-prolonged stress (SPS)-method was used to set up the rat PTSD models. There were six groups:after SPS 1 day,4 days,7 days,14 days,28 days groups and control group. The expressions of caspase-9, Caspase-3 and Cytochrome C proteins were detected with immunohistochemistry, immunofluorescence and Western blotting. Results Immunohistochemical and immunofluorescent results showed that the expression of cytochrome C peaked at 4 days and maintained higher level at 7days after SPS. Expressions of Caspase-9 and Caspase-3 were increased and peaked at 7days after SPS. Western blotting results showed that compared with control group, cytochrome C protein was up-regulated and peaked at 4 days after SPS in the cytosol. Compared with the control group, cytochrome C tended to decrease in mitochondrial fractions. The activated form of Caspase-9 and caspase-3 were not detected in control group. They were present in model groups. Cleaved- caspase-9 and cleaved-caspase-3 peaked at 7 days after SPS, and then gradually decreased at 14 days. Conclusion The neuronal apoptosis in hippocampus of PTSD rats may be one of the causes inducing hippocampus atrophy. Mitochondrial apoptotic pathway is involved in apoptosis in the hippocampus of PTSD rats.
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Objective To observe the expression of cytochrome C (Cyt C)and apoptosis-related gene Bax in hippocampus of posttraumatic stress disorder(PTSD)rats in order to investigate their effects and relationships. Methods Sixty male Wistar rats were used in the present study. The single-prolonged stress(SPS)-method was carried out to set up the rat PTSD models. There were six groups:after SPS 1,4,7,14,28 days groups and control group. The expression of Cyt C and Bax proteins were detected with immunohistochemistry, double immunofluorescence, confocal laser scanning microscopy and Western blotting. Results The expression of Cyt C peaked at 4 days and maintained higher level at 7 days after SPS. At 7 days after SPS, strong immunoreactivity of Bax was noticed,At 14 days after SPS, the expression of Bax was down-regulated and then gradually decreased. Conclusion Bax is upregulated and promotes the releasing of Cyt C. And the releasing of Cyt C may be one of mechanisms of inducing apoptosis in the hippocampus of PTSD rats.
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Objective To investigate expression changes of nuclear receptors-glucocorticoid receptors (GR) in the locus ceruleus neurons of posttraumatic stress disorder(PTSD)like rats. Methods Sixty adult healthy male Wistar rats were enrolled in the experiment. PTSD-like rat model was established by single prolonged stress (SPS). There was no SPS stimulation in the control group and the rats of the other five groups were undisturbedly raised for 24 hours, 4 days,7 days,14 days and 28 days respectively after SPS stimulation.The expressions of glucocorticoid receptors in the locus ceruleus nucleus of all groups were detected with Nissl staining, immunohistochemistry,Western blotting and PCR, and image analysis and statistical analysis were performed. Results GR was distributed in the nucleus of coeruleus neurons, GR expression was showed after 24 hours, 4 days, 7 days treatment and gradually increased, restorative downregulation was seen after 14 days and 28 days, but still high(P<0.05). Conclusion After SPS, the GR locus ceruleus temporarily increased and then lowered, suggesting that PTSD rat locus coeruleus neurons in nuclear receptor-GR expression changes may directly involve in the continuing spirit of PTSD symptoms occurred in the development process.
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Objective To observe the changes of intracellular free calcium and the expression of CaM in the hippocampal neurons of posttraumatic stress disorder (PTSD) rats and to further investigate the neurobiological mechanisms. Methods The SPS-method was used to set up the rat PTSD models. A total of sixty male Wistar rats were randomly divided into 12 hours,1 day,4 days,7 days groups of SPS and normal control group. The intracellular free calcium was examined by fluorescence spectrophotometer. The expression of CaM was detected by using immunohistochemistry, Western blotting and RT-PCR. Results The intracellular free calcium level in the hippocampus of experimental rats was markedly increased 12 hours after SPS stimulation,and reached the peak after 1 day, then gradually decreased to normal level after 7 days. The expression of CaM in the hippocampus 1day after SPS was also the highest and then gradually decreased.Conclusion The lasting dysfunction of Ca~(2+)/CaM signaling cascades in hippocampal may play important roles in the pathogenesis of PTSD rats.
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Objective To investigate relationships between the expression of Bcl-2,Bax protein and neuronal apoptosis in hippocampus of posttraumatic stress disorder(PTSD) rats.Methods The SPS-method was used to set up the rat PTSD models.There were five groups:after SPS 1d,4d,7d,14d groups and control group.Apoptotic cells were detected by electron microscopy and TUNEL method.The expressions of Bcl-2 and Bax proteins were detected with immunohistochemistry,double fluorescent,confocal laser scanning microscopy and Western blotting.Results Apoptotic cells were present in hippocampus of PTSD rats.The number of apoptotic cells increased with the development of PTSD and peaked on the 7th day after SPS,then decreased gradually.The expression of Bcl-2 protein peaked on the 4th day after SPS and Bax protein peaked on the 7th day after SPS,then decreased gradually.The ratio of Bcl-2/Bax increased at the beginning and then gradually decreased.Conclusion The neuronal apoptosis in hippocampus of PTSD rats may be one of reasons inducing hippocampus atrophy.The increase of Bcl-2 and Bax protein and the change of Bcl-2/Bax ratio would play an important role in regulating the hippocampal neuronal survival or death during posttraumatic stress disorder.
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Objective To investigate the interrelation between microtubule associated protein 5 and lysosome in cultured spinal neurons. Methods Neuron culture, immunofluorescence cytochemistry, laser confocal scanning microscope were used. Results In cultured spinal neurons, both of MAP5 and calthepsin D were distributed in cytoplasm and processes. In merged pictures, the distribution of MAP5 and calthepsin D was almost similar. When nocodazole was employed, the distribution of MAP5 and calthepsin D changed simultaneously. Both fluorescence distributed in cytoplasm was uneven and the process was shorter. When PMA was employed, the distribution of red and green fluorescence became reticulum and spread toward membrane. The soma enlarged and the process displayed certain direction accompanying adjacent processes interlinked.Conclusion In cultured spinal neurons, the distributions of MAP5 and lysosomes were almost similar. Both were in cytoplasm and process. Nocodazole and PMA caused reverse change for the distribution of MAP5 and lysosomes. The distribution of MAP5 and calthepsin D treatel with Nocodazole was unregulated, while PMA was regulated and loose. These results suggested that MAP5 and lysosomes were interrelated between structure and function. Both of them were depended on the integrity of microtubule.
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In order to detect the localization of ALPase activity in the liver parenchyma more effectively and make the reaction product finer in EM, AMP (2-amino-2-methyl-1-propanol) buffer has been tried for the exploration on ultrastructural enzyme-histochemistry and biochemical quantitation by the lead citrate method. The microsections were used after fixation with 0.5% glutaraldehyde perfusion.The original Tris-HCl buffer was replaced by 175-350mM AMP buffer and 5mM or 20mM sodium 尾-glycerophosphate were used as substrate. By using all these different concentrations of reaction medium, the ALPase activity in the liver was found in the lateral and sinusoidal surface of hepatocytes as well as in the bile canalicular surface and the surface of mitochondria and lysosome. This suggests that AMP buffer is better and more effective for detection of ALPase activity in liver parenchyma by the lead citrate method.