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
The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place p...The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for along time without affecting total CREB protein levels. The effect of F9204 was similar to morphine whicheffect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitiveN-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phos-phorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also thephosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterationsin the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence.NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.展开更多
Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CS...Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).展开更多
Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DN...Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.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
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The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for along time without affecting total CREB protein levels. The effect of F9204 was similar to morphine whicheffect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitiveN-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phos-phorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also thephosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterationsin the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence.NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.
文摘Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11705064,11675060,and 91730301)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2662016QD005 and 26622018JC017)the Huazhong Agricultural University Scientific and Technological Self-Innovation Foundation Program,China(Grant No.2015RC021)
文摘Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.
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。
