The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central...The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central nervous system in response to sympathetic nervous system activation. In cultured hippocampal neurons, we have previously shown that norepinephrine induces increased expression of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF receptor, TrkB, a transcription factor, and cyclic AMP response element binding protein (CREB). In the present study, we extend these findings of increased BDNF expression to its kinetics of release into the surrounding media. We also evaluate these two cell survival pathways, TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine elicits a more delayed and sustained release of BDNF. In response to both norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across pathways.展开更多
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
文摘The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central nervous system in response to sympathetic nervous system activation. In cultured hippocampal neurons, we have previously shown that norepinephrine induces increased expression of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF receptor, TrkB, a transcription factor, and cyclic AMP response element binding protein (CREB). In the present study, we extend these findings of increased BDNF expression to its kinetics of release into the surrounding media. We also evaluate these two cell survival pathways, TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine elicits a more delayed and sustained release of BDNF. In response to both norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across pathways.
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.
