BACKGROUND:cAMP-response element binding protein(CREB) is a key modulator of various signaling pathways.CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE:...BACKGROUND:cAMP-response element binding protein(CREB) is a key modulator of various signaling pathways.CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE:To investigate the regulatory effects of basic fibroblast growth factor(bFGF) on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN,TIME AND SETTING:An immunohistochemical detection experiment was performed at the Department of Anatomy,Shenyang Medical College,between October 2006 and April 2008. MATERIALS:A total of 60 healthy,adult,Wistar rats were randomly divided into three groups: sham-operated(n=12),ischemia/reperfusion(n=24),and bFGF-treated(n=24).Rabbit anti-rat CREB(1:100) and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company,China.MetaMorph-evolution MP5.0-BX51 microscopy imaging system was provided by China Medical University,China. METHODS:Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion.Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF(500 IU/mL,2 000 IU/kg) or an equal amount of physiological saline.Rats from the sham-operated group underwent a similar surgical procedure,without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES:After 48-hour reperfusion,hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry,and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS:The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons.In the ischemia/reperfusion group,the CREB expression was discrete and neurons were poorly arranged.The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group.The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group(P<0.05),and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group(P<0.05). CONCLUSION:bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.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
Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippoca...Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice.To investigate the effects of entacapone,a modulator of dopamine,on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus,60 mice(7 weeks old)were randomly divided into a vehicle-treated group and the groups treated with 10,50,or 200 mg/kg entacapone.The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition.Immunohistochemical staining results revealed that after entacapone treatment,the numbers of Ki67-positive proliferating cells,doublecortin-positive immature neurons,and phosphorylated cAMP response element-binding protein(pCREB)-positive cells were significantly increased.Western blot analysis results revealed that treatment with tyrosine kinase receptor B(TrkB)receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor(BDNF).Entacapone treatment antagonized the effects of TrkB receptor antagonist.These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway.This study was approved by the Institutional Animal Care and Use Committee of Seoul National University(approval No.SNU-130730-1)on February 24,2014.展开更多
基金Scientific Research Foundation of Liaoning Provincial Education Department for Higher Education Institutions, No.05L442
文摘BACKGROUND:cAMP-response element binding protein(CREB) is a key modulator of various signaling pathways.CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE:To investigate the regulatory effects of basic fibroblast growth factor(bFGF) on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN,TIME AND SETTING:An immunohistochemical detection experiment was performed at the Department of Anatomy,Shenyang Medical College,between October 2006 and April 2008. MATERIALS:A total of 60 healthy,adult,Wistar rats were randomly divided into three groups: sham-operated(n=12),ischemia/reperfusion(n=24),and bFGF-treated(n=24).Rabbit anti-rat CREB(1:100) and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company,China.MetaMorph-evolution MP5.0-BX51 microscopy imaging system was provided by China Medical University,China. METHODS:Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion.Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF(500 IU/mL,2 000 IU/kg) or an equal amount of physiological saline.Rats from the sham-operated group underwent a similar surgical procedure,without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES:After 48-hour reperfusion,hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry,and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS:The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons.In the ischemia/reperfusion group,the CREB expression was discrete and neurons were poorly arranged.The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group.The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group(P<0.05),and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group(P<0.05). CONCLUSION:bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.
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.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIP)(NRF-2016R1A2B4009156)the Promising-Pioneering Researcher Program through Seoul National University(SNU)in 2015 and by the Research Institute for Veterinary Science,Seoul National University.
文摘Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice.To investigate the effects of entacapone,a modulator of dopamine,on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus,60 mice(7 weeks old)were randomly divided into a vehicle-treated group and the groups treated with 10,50,or 200 mg/kg entacapone.The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition.Immunohistochemical staining results revealed that after entacapone treatment,the numbers of Ki67-positive proliferating cells,doublecortin-positive immature neurons,and phosphorylated cAMP response element-binding protein(pCREB)-positive cells were significantly increased.Western blot analysis results revealed that treatment with tyrosine kinase receptor B(TrkB)receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor(BDNF).Entacapone treatment antagonized the effects of TrkB receptor antagonist.These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway.This study was approved by the Institutional Animal Care and Use Committee of Seoul National University(approval No.SNU-130730-1)on February 24,2014.
