Aim Posttraumatic nightmares are a core component of posttraumatic stress disorder （PTSD） and mechanistically linked to the development and maintenance of this disorder, but little is known about their mecha- nism. ...Aim Posttraumatic nightmares are a core component of posttraumatic stress disorder （PTSD） and mechanistically linked to the development and maintenance of this disorder, but little is known about their mecha- nism. Methods We utilized a communication box to establish an animal model of physiological stress （foot-shock I FSI） and psychological stress （PS） to mimic the direct suffering and witnessing of traumatic events. Results Twenty-one days after traumatic stress, some of the experimental animals presented startled awakening （ i. e. , were startled awake by a supposed ＂nightmare＂） with different electroencephalographic spectra features. Our neuroan- atomical results showed that the secondary somatosensory cortex and primary auditory cortex may play an important role in remote traumatic memory retrieval in FS ＂nightmare＂ （FSN） rats, whereas the temporal association cortex may play an important role in PS ＂nightmare＂ （PSN） rats. The FSN and PSN groups possessed common emotion evocation circuits, including activation of the amygdala and inactivation of the infralimbic prefrontal cortex and ven- tral anterior cingulate cortex. The decreased activity of the granular and dysgranular insular cortex was only oh-served in PSN rats. Conclusion The present results imply that different types of stress may cause PTSD-like ＂nightmares＂ in rodents and identified the possible neurocircuitry of memory retrieval and emotion evocation.展开更多
Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- ...Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- rotonin and norepinephrine uptake inhibitor, displayed antidepressant activity more potent and faster than existing antidepressants, which may be clue to the increasing of hippocampal inhibitory serine-phosphorylation of glycogen synthase kinase-3 （GSK3）. The present study was to evaluate whether activation of PI3K/Akt signaling, one of the most important pathways regulating the phosphorylation of GSK3β, was required for ammoxetine induced antide- pressant effects and upregulation of pGSK3β. Behavioral results indicated that acute oral administration of ammoxe- tine at 10 mg/kg produced robust antidepressant effects in the forced swimming test and learned helpless test in mice, which were blocked totally by phosphatidylinositol （PI3）-kinase （PI3K） inhibitor LY294002. Then, West- ern blot results demonstrated that ammoxetine induced increasing of GSK3 β phosphorylation and activation of PI3 K/ Akt signaling can also be antagonized at the same testing time points by LY294002. These findings suggest that ac- tivation of PI3 K/Akt/GSK3[3 signaling is pivotal and necessary for the antidepressant effects of ammoxetine in the forced swimming test and learned helpless test in mice.展开更多
Renal ischemia reperfusion injury increases renal generation of angiotensin II （Ang Ⅱ） which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters ...Renal ischemia reperfusion injury increases renal generation of angiotensin II （Ang Ⅱ） which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters renal af- ferent arteriolar responses to Ang II via production of hydrogen peroxide （ H202 ）, or superoxide （ O2 ） or via al- tered angiotensin type 1 receptor （AT1R） expression. Afferent arterioles of mouse kidneys 24h after renal ischemia repeffusion or sham procedures were isolated and perfused. Responses to Ang II or norepinephrine （NE） were as- sessed by measurement of arteriolar luminal diameter. The mRNA expressions of AT1 receptor （ AT1 R） and AT2 re- ceptor （ATzR） were evaluated by quantificational real-time polymerase chain reaction. Compared to sham group, afferent arterioles from mouse kidneys after renal ischemia reperfusion had impaired contractions to Ang II （ -4.63 ± 3.06） % versus （ - 29.95 ± 1.31 ） % at 10 -9 tool · ^-1, p 〈 0.05 , （ - 27.07 ± 1 50） % versus （ - 41 74 ± 0.60） % at 10^-7 tool · L^-1, P 〈 0.05 ） that were normalized by incubation with PEG-catalase , but unaffected by PEG-SOD. However, the NE responses of afferent arterioles after renal ischemia reperfusion were unchanged. Com- pared to the sham group, renal ischemia reperfusion significantly increased the renal cortical H202 （0. 123 ± -1 0. 006） versus （0. 087 ± 0. 003） mmol·mg protein, P 〈 0.01 ）, reduced catalase activity [ （ 14.81 ± 3.22） ver- sus （28.49 ± 1.62） units · mg^-1 protein, P 〈 0.01 ] and downregulated mRNA for AT1R （0.27 ± 0.02 versus 0.95 ± 0.02, P 〈 0.01 ）. We conclude that afferent arteriolar responses to Ang II are impaired selectively in mice after renal ischemia reperfusion by accumulation of H202 and reduced expression of AT1R.展开更多
文摘Aim Posttraumatic nightmares are a core component of posttraumatic stress disorder （PTSD） and mechanistically linked to the development and maintenance of this disorder, but little is known about their mecha- nism. Methods We utilized a communication box to establish an animal model of physiological stress （foot-shock I FSI） and psychological stress （PS） to mimic the direct suffering and witnessing of traumatic events. Results Twenty-one days after traumatic stress, some of the experimental animals presented startled awakening （ i. e. , were startled awake by a supposed ＂nightmare＂） with different electroencephalographic spectra features. Our neuroan- atomical results showed that the secondary somatosensory cortex and primary auditory cortex may play an important role in remote traumatic memory retrieval in FS ＂nightmare＂ （FSN） rats, whereas the temporal association cortex may play an important role in PS ＂nightmare＂ （PSN） rats. The FSN and PSN groups possessed common emotion evocation circuits, including activation of the amygdala and inactivation of the infralimbic prefrontal cortex and ven- tral anterior cingulate cortex. The decreased activity of the granular and dysgranular insular cortex was only oh-served in PSN rats. Conclusion The present results imply that different types of stress may cause PTSD-like ＂nightmares＂ in rodents and identified the possible neurocircuitry of memory retrieval and emotion evocation.
文摘Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- rotonin and norepinephrine uptake inhibitor, displayed antidepressant activity more potent and faster than existing antidepressants, which may be clue to the increasing of hippocampal inhibitory serine-phosphorylation of glycogen synthase kinase-3 （GSK3）. The present study was to evaluate whether activation of PI3K/Akt signaling, one of the most important pathways regulating the phosphorylation of GSK3β, was required for ammoxetine induced antide- pressant effects and upregulation of pGSK3β. Behavioral results indicated that acute oral administration of ammoxe- tine at 10 mg/kg produced robust antidepressant effects in the forced swimming test and learned helpless test in mice, which were blocked totally by phosphatidylinositol （PI3）-kinase （PI3K） inhibitor LY294002. Then, West- ern blot results demonstrated that ammoxetine induced increasing of GSK3 β phosphorylation and activation of PI3 K/ Akt signaling can also be antagonized at the same testing time points by LY294002. These findings suggest that ac- tivation of PI3 K/Akt/GSK3[3 signaling is pivotal and necessary for the antidepressant effects of ammoxetine in the forced swimming test and learned helpless test in mice.
文摘Renal ischemia reperfusion injury increases renal generation of angiotensin II （Ang Ⅱ） which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters renal af- ferent arteriolar responses to Ang II via production of hydrogen peroxide （ H202 ）, or superoxide （ O2 ） or via al- tered angiotensin type 1 receptor （AT1R） expression. Afferent arterioles of mouse kidneys 24h after renal ischemia repeffusion or sham procedures were isolated and perfused. Responses to Ang II or norepinephrine （NE） were as- sessed by measurement of arteriolar luminal diameter. The mRNA expressions of AT1 receptor （ AT1 R） and AT2 re- ceptor （ATzR） were evaluated by quantificational real-time polymerase chain reaction. Compared to sham group, afferent arterioles from mouse kidneys after renal ischemia reperfusion had impaired contractions to Ang II （ -4.63 ± 3.06） % versus （ - 29.95 ± 1.31 ） % at 10 -9 tool · ^-1, p 〈 0.05 , （ - 27.07 ± 1 50） % versus （ - 41 74 ± 0.60） % at 10^-7 tool · L^-1, P 〈 0.05 ） that were normalized by incubation with PEG-catalase , but unaffected by PEG-SOD. However, the NE responses of afferent arterioles after renal ischemia reperfusion were unchanged. Com- pared to the sham group, renal ischemia reperfusion significantly increased the renal cortical H202 （0. 123 ± -1 0. 006） versus （0. 087 ± 0. 003） mmol·mg protein, P 〈 0.01 ）, reduced catalase activity [ （ 14.81 ± 3.22） ver- sus （28.49 ± 1.62） units · mg^-1 protein, P 〈 0.01 ] and downregulated mRNA for AT1R （0.27 ± 0.02 versus 0.95 ± 0.02, P 〈 0.01 ）. We conclude that afferent arteriolar responses to Ang II are impaired selectively in mice after renal ischemia reperfusion by accumulation of H202 and reduced expression of AT1R.
