The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swi...The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.展开更多
The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs ...The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.展开更多
Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place ...Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.展开更多
Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Ab...Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Abeta) in vitro and its effects on nuclear factor-κB (NF-κB) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique. Methods: B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 (Aβ 1-40, 10 μmol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (Aβ 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 (5 μmo/L) for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results: Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P〈0.05, P〈0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells (P〈0.05, P〈0.01). Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression (P〈0.01). Conclusions: Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.展开更多
cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)在神经元生成、突触可塑性及学习记忆等方面都具有重要的调节作用,这使得与CREB信号通路相关的分子成为较受关注的神经系统疾病干预的药物靶点.本文概述了CREB的基本...cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)在神经元生成、突触可塑性及学习记忆等方面都具有重要的调节作用,这使得与CREB信号通路相关的分子成为较受关注的神经系统疾病干预的药物靶点.本文概述了CREB的基本构成、相关信号通路、其目的基因表达调控及其在阿尔茨海默病(Alzheimer’s disease,AD)中的作用.展开更多
目的:探讨微小RNA-302c(miR-302c)在肺癌组织中的表达,以及对肺癌侵袭和迁移的影响和作用机制。方法:在线分析GEO数据库中GSE19945和GSE136043两组肺癌数据集中miR-302c的表达情况,通过Human Protein Atlas数据库研究CREB1表达情况;双...目的:探讨微小RNA-302c(miR-302c)在肺癌组织中的表达,以及对肺癌侵袭和迁移的影响和作用机制。方法:在线分析GEO数据库中GSE19945和GSE136043两组肺癌数据集中miR-302c的表达情况,通过Human Protein Atlas数据库研究CREB1表达情况;双荧光素酶实验证明miR-302c和CREB1的关系。正常组细胞不加任何药物,对照组细胞转染miR-302cmimic-NC,实验组细胞转染miR-302c-mimic。通过Transwell小室检测细胞的侵袭与迁移能力,通过小管形成检测细胞的血管生成能力,通过Western blot检测各组细胞中CREB1、p-P53、p-P21的表达水平。结果:生物信息分析显示,与正常组织相比,miR-302c在肺癌组织、肺癌淋巴转移组织中的表达明显降低,肺癌组织中CREB1的表达明显升高;双荧光素酶实验证明miR-302c靶向调控CREB1的表达;与正常组相比,实验组迁移和侵袭的细胞数量、小管生成的数量明显下降,实验组中CREB1的表达明显下降,p-P53、p-P21的表达明显升高(均P<0.05)。结论:miR-302c在肺癌组织表达降低,过表达miR-302c后能明显抑制肺癌细胞的侵袭与转移,这可能与抑制靶基因CREB1的表达,以及激活P53信号通路有关。展开更多
目的观察松郁安神方对异相睡眠剥夺(PSD)大鼠海马环磷酸腺苷反应元件结合蛋白(CREB)的影响。方法采用改良多平台睡眠剥夺法建立PSD大鼠模型,连续7 d用松郁安神方进行灌胃。RT-PCR和蛋白印迹法检测对照组、PSD模型组、中药高、低剂量组...目的观察松郁安神方对异相睡眠剥夺(PSD)大鼠海马环磷酸腺苷反应元件结合蛋白(CREB)的影响。方法采用改良多平台睡眠剥夺法建立PSD大鼠模型,连续7 d用松郁安神方进行灌胃。RT-PCR和蛋白印迹法检测对照组、PSD模型组、中药高、低剂量组大鼠海马CREB m RNA和蛋白表达的情况。结果与对照组比较,PSD模型组大鼠海马CREB m RNA及蛋白表达均明显降低(P<0.01),不同剂量松郁安神方干预后,中药高剂量组CREB m RNA及蛋白表达明显升高(P<0.01),中药低剂量组CREB m RNA表达升高(P<0.05),蛋白表达也明显升高(P<0.01)。结论松郁安神方改善PSD大鼠学习记忆能力的机制可能与调节海马CREB的表达有关。展开更多
基金supported by the National Natural Science Foundation of China,No.30973782the National Natural Science Foundation for the Youth,No.81001693+1 种基金the Natural Science Foundation of Beijing,No.7102014,7122018the Science and Technology Foundation for Chinese Medicine in Beijing,No.JJ2008-042
文摘The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.
基金supported by the National Natural Science Foundation of China,No.81202620the Domestic Visiting Scholar Program for Young Talent Teachers in University of Shandong Province
文摘The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.
文摘Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.
文摘Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Abeta) in vitro and its effects on nuclear factor-κB (NF-κB) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique. Methods: B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 (Aβ 1-40, 10 μmol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (Aβ 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 (5 μmo/L) for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results: Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P〈0.05, P〈0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells (P〈0.05, P〈0.01). Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression (P〈0.01). Conclusions: Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.
文摘目的:探讨微小RNA-302c(miR-302c)在肺癌组织中的表达,以及对肺癌侵袭和迁移的影响和作用机制。方法:在线分析GEO数据库中GSE19945和GSE136043两组肺癌数据集中miR-302c的表达情况,通过Human Protein Atlas数据库研究CREB1表达情况;双荧光素酶实验证明miR-302c和CREB1的关系。正常组细胞不加任何药物,对照组细胞转染miR-302cmimic-NC,实验组细胞转染miR-302c-mimic。通过Transwell小室检测细胞的侵袭与迁移能力,通过小管形成检测细胞的血管生成能力,通过Western blot检测各组细胞中CREB1、p-P53、p-P21的表达水平。结果:生物信息分析显示,与正常组织相比,miR-302c在肺癌组织、肺癌淋巴转移组织中的表达明显降低,肺癌组织中CREB1的表达明显升高;双荧光素酶实验证明miR-302c靶向调控CREB1的表达;与正常组相比,实验组迁移和侵袭的细胞数量、小管生成的数量明显下降,实验组中CREB1的表达明显下降,p-P53、p-P21的表达明显升高(均P<0.05)。结论:miR-302c在肺癌组织表达降低,过表达miR-302c后能明显抑制肺癌细胞的侵袭与转移,这可能与抑制靶基因CREB1的表达,以及激活P53信号通路有关。
文摘目的观察松郁安神方对异相睡眠剥夺(PSD)大鼠海马环磷酸腺苷反应元件结合蛋白(CREB)的影响。方法采用改良多平台睡眠剥夺法建立PSD大鼠模型,连续7 d用松郁安神方进行灌胃。RT-PCR和蛋白印迹法检测对照组、PSD模型组、中药高、低剂量组大鼠海马CREB m RNA和蛋白表达的情况。结果与对照组比较,PSD模型组大鼠海马CREB m RNA及蛋白表达均明显降低(P<0.01),不同剂量松郁安神方干预后,中药高剂量组CREB m RNA及蛋白表达明显升高(P<0.01),中药低剂量组CREB m RNA表达升高(P<0.05),蛋白表达也明显升高(P<0.01)。结论松郁安神方改善PSD大鼠学习记忆能力的机制可能与调节海马CREB的表达有关。