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Effects of Exposure to Aluminum on Long-term Potentiation and AMPA Receptor Subunits in Rats in vivo 被引量:14
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作者 SONG Jing LIU Ying +2 位作者 ZHANG Hui Fang ZHANG Qin Li NIU Qiao 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2014年第2期77-84,共8页
Objective To explore the effects of exposure to aluminum (AI) on long-term potentiation (LTP) and AMPA receptor subunits in rats in vivo. Methods Different dosages of aluminum-maltolate complex [Al(mal)3] were g... Objective To explore the effects of exposure to aluminum (AI) on long-term potentiation (LTP) and AMPA receptor subunits in rats in vivo. Methods Different dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection and subchronic intraperitoneal (i.p.) injection. Following AI exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins (GluR1 and GluR2) in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay. Results Acute AI treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluRz and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic AI treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits. Conclusion Al(mal)3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation. 展开更多
关键词 Aluminum-maltolate complex Long-term potentiation ampa receptor HIPPOCAMPUS INVIVO
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Induction of Increased Intracellular Calcium in Astrocytes by Glutamate through Activating NMDA and AMPA Receptors 被引量:1
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作者 张蕲 胡波 +1 位作者 孙圣刚 童萼塘 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2003年第3期254-257,共4页
To study the effect of glutamate on the intracellular calcium signal of pure cultured rat astrocytes and the role of NMDA and AMPA receptors in the procedure, the change of calcium signal was investigated by monitorin... To study the effect of glutamate on the intracellular calcium signal of pure cultured rat astrocytes and the role of NMDA and AMPA receptors in the procedure, the change of calcium signal was investigated by monitoring the fluctuation of intracellular Ca 2+ concentration ([Ca 2+ ] i) on the basis of Fura-2 single cell fluorescent ratio (F345/F380). The changes in the effect of glutamate on the intracellular calcium signal were observed after blockage of NMDA and(or) AMPA receptors. It was found that L-glutamate could induce an increased [Ca 2+ ] i in most of the cells in concentration- and time-dependent manner. D-(-)-2-amino-5-phosphonopentanoic acid (D-AP-5, a selective antagonist of the NMDA receptor) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, a selective antagonist of the AMPA receptor) could abolish the effects of NMDA and AMPA respectively. The treatment of D-AP-5 and CNQX simultaneously or respectively could attenuate the effect of L-glutamate at varying degrees. All these indicated that glutamate could modulate intracellular Ca 2+ of pure cultured rat astrocytes through different pathways. The activation of NMDA and AMPA receptors took part in the complex mechanisms. 展开更多
关键词 GLUTAMATE ASTROCYTES NMDA receptor ampa receptor [Ca 2+] i
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Mechanism and impact of a novel allosteric AMPA receptor modulator on protection against respiratory depression 被引量:1
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作者 Wei DAI Xiang GAO +2 位作者 Yu-lei LI Zheng YONG Rui-bin SU 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2018年第4期276-277,共2页
OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hyp.notics.To explore the mechanism of LCX001 on protection against respiratory depression,a novel AMPA receptor modulator LCX001,synthesiz... OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hyp.notics.To explore the mechanism of LCX001 on protection against respiratory depression,a novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration.METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid(fentanyl and TH-030418),propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation.The function of AMPA receptors were determined by location of receptors in the membrane and state of channel opening,and both processes were impressed by AMPA receptor regulatory proteins.Ac.cording to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by west.ern blotting.The variation of receptor surface location was observed by live cell imaging.The regula.tion on neuronal Ca^(2+) and cell function was investigated intensively by Ca^(2+) imaging to clarify mecha.nism of LCX001.RESULTS LCX001 effectively rescued and prevented opioid(fentanyl and TH-030418),propofol,and pentobarbital-induced respiratory depression by strengthening respiratory fre.quency and minute ventilation in rats.The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001,in contrast to some ampakines that did not affect analgesia.Fur.thermore,LCX001 potentiated [3 H]AMPA and L-glutamate binding affinity to AMPA receptors,and facili.tated glutamate-evoked inward currents in HEK293 cells stably expressing GluA2(R).Importantly,appli.cation of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioid-induced abnormal intracellular Ca^(2+) load,which might par.ticipate in breathing modulation.CONCLUSION The novel pharmacological effect and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respi.ratory depression. 展开更多
关键词 麻醉药 镇静催眠药 临床分析 治疗方法
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Protection against respiratory depression by novel allosteric AMPA receptor modulator
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作者 DAI Wei GAO Xiang +2 位作者 LI Yu-lei YONG Zheng SU Rui-bin 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2018年第9期735-736,共2页
OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hypnotics.For emergency use,specific antagonists are currently administered to counteract respiratory depression.However,antagonists are of... OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hypnotics.For emergency use,specific antagonists are currently administered to counteract respiratory depression.However,antagonists are often short-lasting and can have multiple unexpected side effects.A novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration.To explore the mechanism and impact of LCX001 on protection against respiratory depression.METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid,propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate potential analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation.The function of AMPA receptors were determined by location of receptors inthe membrane and state of channel opening,and both processes were impressed by AMPA receptor regulatory proteins.According to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by Western blotting.The variation of receptor surface location were observed by live cell imaging.The regulation on neuronal Ca2+and cell function was investigated intensively by Ca2+imaging to clarify mechanism of LCX001.RESULTS LCX001 effectively rescued and prevented opioid(fentanyl and TH-030418),propofol,and pentobarbitalinduced respiratory depression by strengthening respiratory frequency and minute ventilation by 30%-50% in rats.The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001 on increasing the inhibition rate and %MPE to 80% and 65% respectively,in contrast to some ampakines that did not affect analgesia.Furthermore,LCX001 potentiated[3 H]AMPA and L-glutamate binding affinity to AMPA receptors,and facilitated glutamateevoked inward currents in HEK293 cells stably expressing GluA2(R).At 10 mmol·L^(-1) glutamate evoked amplitudes,LCX001 at 100 μmol·L^(-1) increased the potency of glutamate induced currents by(1120 ± 60) pA,compared with that of(752 ± 35) pA in the control group.LCX001 also prominently promoted steady state/peak amplitude ratio.LCX001 significantly slowed down the desensitization rates of the AMPA ion channel,and inhibited current decay.Importantly,application of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioidinduced abnormal intracel ular Ca2+load,which might participate in breathing modulation.CONCLUSION The typical positive modulatory impact and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respiratory depression. 展开更多
关键词 RESPIRATORY DEPRESSION GLUTAMATE ampa receptor MODULATOR
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基于AMPA受体和神经电生理分析拉莫三嗪治疗癫痫的效果
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作者 黄媛媛 李直 +1 位作者 胡海琼 李佳敏 《中国实用神经疾病杂志》 2024年第9期1112-1116,共5页
目的基于α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体和神经电生理变化分析拉莫三嗪治疗癫痫的效果。方法选取2022-08—2023-12四川省南充精神卫生中心神经内科收治的82例癫痫患者为对象,随机分为对照组41例和观察组41例。对照组予... 目的基于α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体和神经电生理变化分析拉莫三嗪治疗癫痫的效果。方法选取2022-08—2023-12四川省南充精神卫生中心神经内科收治的82例癫痫患者为对象,随机分为对照组41例和观察组41例。对照组予以丙戊酸钠治疗,观察组予以拉莫三嗪治疗,统计2组临床疗效及不良反应发生情况,比较2组患者治疗前后AMPA受体水平和神经电生理变化情况。结果观察组临床总有效率高于对照组(P<0.05)。治疗3、6个月后,2组AMPA受体水平明显低于治疗前(P<0.05),且观察组低于对照组(P<0.05);2组θ、δ、α频率稳定情况明显优于治疗前(P<0.05),且观察组优于对照组(P<0.05);2组θ、δ、α波段相对功率比较无统计学差异(P>0.05)。观察组不良反应发生率较对照组低(P<0.05)。结论拉莫三嗪治疗癫痫的疗效确切,安全性较高。通过检测患者AMPA受体水平、监测脑电图变化情况可对拉莫三嗪治疗癫痫的疗效作出有效评估。 展开更多
关键词 癫痫 ampa受体 神经电生理 拉莫三嗪 脑电图
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AMPA受体亚基GluA4在脑功能和神经精神疾病中的作用
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作者 张珺 夏宇杰 +3 位作者 杨咏琪 王丽媛 何悦 刘艳玲 《赣南医学院学报》 2024年第5期464-469,共6页
AMPA受体(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor,AMPAR)亚基GluA4在不同脑区、不同类型细胞的表达具有时间特异性,GluA4同四聚体受体具有高Ca2+通透性和亚毫秒级的门控动力学,是快速突触反应和高保真神经传... AMPA受体(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor,AMPAR)亚基GluA4在不同脑区、不同类型细胞的表达具有时间特异性,GluA4同四聚体受体具有高Ca2+通透性和亚毫秒级的门控动力学,是快速突触反应和高保真神经传递的基础,在神经环路形成及神经信息传递等脑功能中发挥重要作用。越来越多的研究表明,GluA4表达异常可能会扰乱神经环路的放电节律,阻碍神经信息传递以及损害学习记忆,导致癫痫、阿尔茨海默病等神经精神疾病的发生。本文对GluA4在脑正常生理功能和抑郁症、阿尔茨海默病、精神分裂症、癫痫等神经精神疾病中的作用进行综述。 展开更多
关键词 ampa受体 GluA4 突触可塑性 神经精神疾病
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S-palmitoylation regulates AMPA receptors trafficking and function: a novel insight into synaptic regulation and therapeutics 被引量:7
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作者 Jun Han Pengfei Wu +1 位作者 Fang Wang Jianguo Chen 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2015年第1期1-7,共7页
Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translatio... Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases. 展开更多
关键词 PALMITOYLATION ampa receptors TRAFFICKING DHHC
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Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain 被引量:4
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作者 ZHANG Yue-lin ZHANG Peng-bo +3 位作者 QIU Shu-dong LI Yong TIAN Ying-fang WANG Ying 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第18期1555-1562,共8页
Background Activation of N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl- 4-isoxazole-propionic acid (AMPA) receptors play an important role in the neurons death induced by ischemia. The m... Background Activation of N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl- 4-isoxazole-propionic acid (AMPA) receptors play an important role in the neurons death induced by ischemia. The mitigating effect of intravenous anesthetics on ischemic neuron injury is related to their influence on NMDA receptors. This study was performed to investigate the effect of ketamine-midazolam anesthesia on the NMDA and AMPA receptor subunits expression in the peri-infarction of ischemic rat brain and explore its potential mechanism of neuroprotection. Methods Thirty Sprague Dawley (SD) rats were subjected to permanent middle cerebral artery occlusion under ketamine/atropine (100/0.05 mg/kg) or ketamine-midazolam/atropine (60/50/0.05 mg/kg) intraperitoneal anesthesia (n=15 each). Twenty-four hours after ischemia, five rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally and infarct size was measured. Twenty-four and 72 hours after ischemia, four rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally. After staining the brain tissue slices with toluidine blue, the survived neurons in the peri-infarction were observed. Also, the expression level of NMDA receptors 1 (NR1), NMDA receptors 2A (NR2A), NMDA receptors 2B (NR2B) and AMPA (GluR1 subunit) were determined by grayscale analysis in immunohistochemical stained slices. Results Compared with ketamine anesthesia, ketamine-midazolam anesthesia produced not only smaller infarct size [(24.1±4.6)% vs (38.4±4.2)%, P〈0.05], but also higher neuron density (24 hours: 846±16 vs 756±24, P〈0.05; 72 hours: 882±22 vs 785± 18, P〈0.05) and lower NR2A (24 hours: 123.0±4.9 vs 95.0±2.5, P〈 0.05; 72 hours: 77.8±4.1 vs 54.2±3.9, P〈0.05) and NR2B (24 hours: 98.5±2.7 vs 76.3±2.4, P〈0.05; 72 hours: 67.2±7.5 vs 22.2± 2.6, P〈0.05) expression level in the peri-infarction following ischemia. Conclusion The protective effects of ketamine-midazolam anesthesia on ischemic brain injury may relate to decreasing NR2A and NR2B expression. 展开更多
关键词 KETAMINE MIDAZOLAM cerebral ischemia NMDA receptor ampa receptor
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Mechanism-based design of 2,3-benzodiazepine inhibitors for AMPA receptors
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作者 Li Niun 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2015年第6期500-505,共6页
2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule antagonists of(R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptors.Antagonists of AMPA receptors ... 2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule antagonists of(R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptors.Antagonists of AMPA receptors are drug candidates for potential treatment of a number of neurological disorders such as epilepsy,stroke and amyotrophic lateral sclerosis(ALS).How to make better inhibitors,such as 2,3-BDZs,has been an enduring quest in drug discovery.Among a few available tools to address this specific question for making better 2,3-BDZs,perhaps the best one is to use mechanistic clues from studies of the existing antagonists to design and discover more selective and more potent antagonists.Here I review recent work in this area,and propose some ideas in the continuing effort of developing newer 2,3-BDZs for tighter control of AMPA receptor activities in vivo. 展开更多
关键词 ampa receptors 2 3-Benzodiazepine derivatives Subunit-selective antagonists RNA aptamers
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产前应激对子代大鼠海马CA1区AMPA受体表达的影响
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作者 郑瑞霞 冯慧 《菏泽医学专科学校学报》 2023年第3期1-4,共4页
目的探讨产前应激对子代大鼠海马CA1区AMPA受体蛋白表达的影响。方法建立产前应激模型,随机选取子代以强迫游泳实验验证抑郁样行为,并通过免疫组化技术观察产前应激对子代大鼠海马CA1区AMPA受体蛋白表达的差异。结果强迫游泳结果发现,... 目的探讨产前应激对子代大鼠海马CA1区AMPA受体蛋白表达的影响。方法建立产前应激模型,随机选取子代以强迫游泳实验验证抑郁样行为,并通过免疫组化技术观察产前应激对子代大鼠海马CA1区AMPA受体蛋白表达的差异。结果强迫游泳结果发现,产前应激可明显增强子代大鼠的不动时间,表现出明显的抑郁样行为;并且产前应激可导致子代大鼠海马CA1区GluA1-3亚基表达降低,但是对GluA4亚基表达没有影响。结论产前应激导致子代大鼠抑郁样行为与GluA1-3亚基表达降低有关。 展开更多
关键词 产前应激 子代 海马 ampa受体
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AMPA受体和相关蛋白在束缚应激大鼠相关脑区的表达变化及逍遥散对其影响 被引量:11
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作者 岳广欣 王竹风 +4 位作者 张巧丽 赵歆 岳利峰 丁杰 陈家旭 《中国应用生理学杂志》 CAS CSCD 北大核心 2008年第2期129-132,共4页
目的:观察海马及杏仁核α-氨基羟甲基恶唑丙酸(AMPA)受体亚基和相关调节蛋白在束缚应激状态下蛋白表达变化及逍遥散的调节作用。方法:使用每天捆绑3 h的方法制作慢性束缚应激动物模型,并用逍遥散进行干预,分别于7 d后和21 d后用Western ... 目的:观察海马及杏仁核α-氨基羟甲基恶唑丙酸(AMPA)受体亚基和相关调节蛋白在束缚应激状态下蛋白表达变化及逍遥散的调节作用。方法:使用每天捆绑3 h的方法制作慢性束缚应激动物模型,并用逍遥散进行干预,分别于7 d后和21 d后用Western blot方法检测各组大鼠海马CA1区、CA3区、齿状回(DG)和杏仁核的AMPA受体亚基GluR2/3及N-乙基顺丁烯二酰亚胺敏感性的融合蛋白(NSF)、PKC作用蛋白1(PICK1)蛋白表达的情况。结果:7 d应激可使DG和杏仁核的GluR2/3、NSF表达显著降低(P均<0.05),使PICK1在CA1区的表达量显著增多(P<0.05),逍遥散对PICK1变化显示出一定调节作用。21 d应激可使CA1区的GluR2/3、NSF表达升高,其中GluR2/3有显著性差异(P<0.01),而在杏仁核表达有降低趋势,逍遥散对其均有显著调节作用(均为P<0.05),21 d应激使杏仁核PICK1表达量出现升高趋势,逍遥散可显著降低其表达(P<0.05)。结论:AMPA受体在短期重复应激和慢性应激状态下反应不同,海马和杏仁核反应相反,逍遥散对慢性应激状态下AMPA受体表达的调节作用较短期重复应激强。 展开更多
关键词 束缚应激 突触可塑性 Western blot ampa受体 NSF PICK1 逍遥散
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AMPA对吸入麻醉药催眠、镇痛作用的影响 被引量:7
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作者 杭黎华 邵东华 +3 位作者 杨映红 施蕾蕾 戴体俊 曾因明 《中国药理学通报》 CAS CSCD 北大核心 2007年第12期1571-1575,共5页
目的探讨AMPA(α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid,AMPA)对吸入麻醉药恩氟烷、异氟烷、七氟烷催眠、镇痛作用的影响。方法建立小鼠腹腔注射吸入麻醉药催眠、镇痛模型,在催眠和热板法实验中分别观察侧脑室(intracer... 目的探讨AMPA(α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid,AMPA)对吸入麻醉药恩氟烷、异氟烷、七氟烷催眠、镇痛作用的影响。方法建立小鼠腹腔注射吸入麻醉药催眠、镇痛模型,在催眠和热板法实验中分别观察侧脑室(intracerebroventricular,icv)或鞘内(intrathecal,it)注射不同剂量的AMPA对小鼠睡眠时间(sleep time,ST)和热板法痛阈值(pain threshold in hot-plate test,HPPT)的影响。结果催眠实验中,AMPA50、75、100ng组的ST与aCSF组相比,差异无统计学意义(P>0.05)。镇痛实验中,aCSF及AMPA0.25、0.5、1.0ng it对正常对照组小鼠的HPPT均无影响(P>0.05)。AMPA0.25、0.5、1.0ng it剂量依赖性地降低吸入麻醉药镇痛小鼠的HPPT(P<0.05或P<0.01)。结论脑内的AMPA受体与吸入麻醉药恩氟烷、异氟烷、七氟烷催眠作用的关系不大,脊髓的AMPA受体参与了吸入麻醉药恩氟烷、异氟烷、七氟烷的镇痛作用。 展开更多
关键词 ampa受体 吸入麻醉药 催眠 镇痛 机制
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应激性抑郁样行为发生中海马5-羟色胺1A受体的作用及其对NMDA受体和AMPA受体的调节 被引量:18
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作者 问黎敏 安书成 刘慧 《心理学报》 CSSCI CSCD 北大核心 2012年第10期1318-1328,共11页
为探讨慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A,5-HT1AR)表达与作用,及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA... 为探讨慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A,5-HT1AR)表达与作用,及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA)受体的影响。通过建立CUMS动物模型,给应激抑郁模型大鼠海马微量注射5-HT1A受体激动剂、给正常大鼠海马微量注射5-HT1A受体拮抗剂,测量大鼠体重变化率,并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测,运用Western blot和ELISA方法检测大鼠海马组织中5-HT1AR和NMDAR和AMPAR的关键亚基的表达以及磷酸化水平。结果显示,与对照组相比,CUMS组大鼠表现出抑郁样行为,海马5-HT1AR、AMPA受体的GluR2/3亚基表达及磷酸化明显降低,NMDA受体的NR1和NR2B亚基表达及磷酸化显著增加;正常大鼠海马微量注射5-HT1A受体拮抗剂WAY100635,动物行为学表现及AMPA受体、NMDA受体表达及磷酸化水平均与CUMS组相同;注射5-HT1A受体激动剂8-OH-DPAT能逆转应激诱导的上述改变。以上结果表明,CUMS诱发抑郁样行为与海马5-HT1AR表达下降,AMPAR表达量及磷酸化水平降低,NMDAR表达量及磷酸化水平升高有关。5-HT通过5-HT1AR产生抗抑郁作用。5-HT1AR激动剂抗抑郁作用与降低NMDAR表达量及磷酸化水平,提高AMPAR表达量及磷酸化水平密切相关。 展开更多
关键词 慢性不可预见性温和应激 抑郁症 海马 5-HT1A受体 NMDA受体 ampa受体
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海仁酸致痫大鼠海马组织AMPA受体GluR2表达的变化 被引量:8
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作者 魏瑛 刘子建 +1 位作者 朱长庚 刘庆莹 《中国组织化学与细胞化学杂志》 CAS CSCD 2003年第3期302-305,共4页
目的 为了研究AMPA受体在癫痫发生中的作用。方法 本研究用免疫组织化学方法观察了海仁酸致痫大鼠海马组织AMPA GluR2受体的表达变化。结果 在侧脑室注射海仁酸后 1h ,4h ,12h ,2 4h及 7d ,大鼠海马CA3区及齿状回GluR2的表达明显减... 目的 为了研究AMPA受体在癫痫发生中的作用。方法 本研究用免疫组织化学方法观察了海仁酸致痫大鼠海马组织AMPA GluR2受体的表达变化。结果 在侧脑室注射海仁酸后 1h ,4h ,12h ,2 4h及 7d ,大鼠海马CA3区及齿状回GluR2的表达明显减弱 ,显微图像分析 :与对照组相比 ,KA 4h ,KA 12h ,KA 2 4h ,KA 7d组大鼠海马组织GluR2阳性神经元平均光密度值降低 ,差异有显著性 (P <0 0 5 )。结论 在癫痫发作过程中AMPA受体 GluR2亚单位表达改变可能与癫痫发作导致的神经元损伤有密切关系。 展开更多
关键词 海仁酸 癫痫 使君子酸受体 大鼠 ampa受体 GLUR2 表达 神经元损伤
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缺氧所致神经元AMPA受体的结构组成及功能变化 被引量:5
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作者 刘宝松 陈恒胜 +3 位作者 许忠 陈力学 曾琳 龙在云 《第三军医大学学报》 CAS CSCD 北大核心 2004年第23期2139-2142,共4页
目的 探讨缺氧损伤后神经元膜表面谷氨酸AMPA受体亚单位 (GluRs)含量、受体结构组成、功能的变化及其在Ca2 + 超载和延迟性细胞死亡中的作用。方法 建立神经元缺氧损伤模型 ,采用PI染色、双重免疫荧光标记和细胞比色分析技术定量观察... 目的 探讨缺氧损伤后神经元膜表面谷氨酸AMPA受体亚单位 (GluRs)含量、受体结构组成、功能的变化及其在Ca2 + 超载和延迟性细胞死亡中的作用。方法 建立神经元缺氧损伤模型 ,采用PI染色、双重免疫荧光标记和细胞比色分析技术定量观察神经元死亡和膜表面GluRs含量变化 ,采用Fura 2法测定胞内Ca2 + 含量 ,以膜片钳技术检测微兴奋性突触后电流 (mEPSCs)的变化。结果 伤后胞内Ca2 + 含量和神经元死亡数量明显高于对照组 ;膜表面GluR2含量及含GluR2的突触数目显著减少 (P <0 .0 5 ) ,而GluR3含量较对照组则显著升高 (P <0 0 5 ) ;缺乏GluR2的AMPA受体通道对Ca2 + 有很高的通透性。结论 缺氧可致神经元膜表面AMPA受体的结构组成发生变化 ,缺乏GluR2的受体通道数目增加 ,介导了Ca2 + 的快速内流 ,引起神经元的延迟性死亡。 展开更多
关键词 GLUR2 ampa受体 mEPSCs CA^2+
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AMPA受体介导氯胺酮抗抑郁大鼠海马BDNF及TrkB变化 被引量:5
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作者 杨春 李文媛 +5 位作者 张广芬 徐世霞 余海鹰 高志勤 杨建军 徐建国 《临床麻醉学杂志》 CAS CSCD 北大核心 2011年第11期1101-1103,共3页
目的观察α-氨基-3-羟基-5-甲基-4-异恶唑(AMPA)受体介导氯胺酮抗抑郁过程中大鼠海马脑源性神经营养因子(BDNF)及酪氨酸受体激酶B(TrkB)的表达变化。方法 80只Wistar雄性大鼠随机均分为八组:第一部分包括二甲基亚砜(DMSO)+生理盐水(V1组... 目的观察α-氨基-3-羟基-5-甲基-4-异恶唑(AMPA)受体介导氯胺酮抗抑郁过程中大鼠海马脑源性神经营养因子(BDNF)及酪氨酸受体激酶B(TrkB)的表达变化。方法 80只Wistar雄性大鼠随机均分为八组:第一部分包括二甲基亚砜(DMSO)+生理盐水(V1组)、DMSO+氯胺酮(V2组)、AMPA受体阻断剂(NBQX)5mg/kg+氯胺酮(N5组)、NBQX10mg/kg+氯胺酮(N10组);第二部分包括DMSO+酒精+生理盐水(V3组)、DMSO+酒精+氯胺酮(V4组)、AMPA受体激动剂(CX546)1mg/kg+生理盐水(C0组)、CX5461mg/kg+氯胺酮组(C1组)。干预前1d大鼠强迫游泳15min,干预当天分别进行DMSO、NBQX及CX546预处理,30min后给予1ml生理盐水或氯胺酮10mg/kg。第2次给药后30min强迫游泳,记录5min内不动时间,随后取海马组织检测BDNF及TrkB表达。结果与V2组比较,N5组及N10组大鼠强迫游泳不动时间增加,海马BD-NF、TrkB表达减少(P<0.05)。与V4组比较,C1组大鼠强迫游泳不动时间减少,海马BDNF、TrkB表达增加(P<0.05)。结论 AMPA受体介导氯胺酮抗抑郁作用,这可能与海马组织中BDNF和TrkB表达上调有关。 展开更多
关键词 氯胺酮 抑郁 ampa受体 脑源性神经营养因子 酪氨酸受体激酶B 海马
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Tau蛋白过度磷酸化对突触后膜AMPA受体数量及功能的影响 被引量:5
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作者 林杭 王伟文 +1 位作者 李薇 杨正辉 《中国老年学杂志》 CAS CSCD 北大核心 2013年第21期5364-5366,共3页
目的 探讨大鼠Tau蛋白过度磷酸化对突触后膜AMPA受体数量及功能的影响.方法 原代培养新生SD大鼠海马神经元,将编码红色荧光蛋白DsRed的质粒(标记树突棘)和绿色荧光蛋白GFP标记的P301L突变的人类Tau蛋白基因共转染到5~7d的原代培养大... 目的 探讨大鼠Tau蛋白过度磷酸化对突触后膜AMPA受体数量及功能的影响.方法 原代培养新生SD大鼠海马神经元,将编码红色荧光蛋白DsRed的质粒(标记树突棘)和绿色荧光蛋白GFP标记的P301L突变的人类Tau蛋白基因共转染到5~7d的原代培养大鼠海马神经元内持续培养,编码DsRed的质粒和野生型GFP-Tau共转染为对照.以神经活细胞实时图像成像分析Tau蛋白易位过程.以免疫组化分别检测各组Tau蛋白的表达及AMPA受体数量改变.结果 野生型GFP-Tau蛋白组只出现在树突上,GFP-P301L突变组Tau蛋白广泛出现于树突棘上;与野生型组相比,GFP-P301L突变组Tau蛋白表达水平显著增加(P<0.01),AMPA受体数量显著减少(P<0.01).结论 Tau蛋白过度磷酸化可能通过显著减少AMPA受体数量,导致AMPA受体在突触后膜上的运输失常,造成认知功能的障碍. 展开更多
关键词 TAU蛋白过度磷酸化 ampa受体 突触后膜
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AMPA受体正向变构调节剂的研究进展 被引量:2
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作者 范於菟 徐金林 +4 位作者 王琦瓅 武祥龙 王慧 刘祈星 梅其炳 《化学试剂》 CAS 北大核心 2016年第2期129-136,共8页
AMPA受体是离子型谷氨酸受体中重要的一类亚型,在中枢神经系统中发挥重要作用,是治疗神经精神系统障碍性疾病的重要靶点,受到越来越多学者的关注。AMPA受体正向变构调节剂成为治疗上述疾病的药物研发的热点。对近年来小分子AMPA受体正... AMPA受体是离子型谷氨酸受体中重要的一类亚型,在中枢神经系统中发挥重要作用,是治疗神经精神系统障碍性疾病的重要靶点,受到越来越多学者的关注。AMPA受体正向变构调节剂成为治疗上述疾病的药物研发的热点。对近年来小分子AMPA受体正向变构调节剂的研究进展进行了综述。 展开更多
关键词 ampa受体 正向变构调节剂 阿尔茨海默氏症 合成 构效关系
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AMPA受体的内化及其分子机制 被引量:3
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作者 郑婵颖 罗建红 赵卉 《细胞生物学杂志》 CSCD 北大核心 2004年第3期216-220,共5页
AMPA受体的内化不仅仅是结束它们的活性状态,受体的许多重要信号功能是与活性依赖的内化密切相关的。突触功能调节中,存在2种形式AMPA受体的内化:组构性内化和活性依赖的内化。现就AMPA受体内化的分类、过程和意义,以及活性依赖的内化... AMPA受体的内化不仅仅是结束它们的活性状态,受体的许多重要信号功能是与活性依赖的内化密切相关的。突触功能调节中,存在2种形式AMPA受体的内化:组构性内化和活性依赖的内化。现就AMPA受体内化的分类、过程和意义,以及活性依赖的内化的诱发因素、调节因素和内化后的去向进行综述。 展开更多
关键词 ampa受体 分子机制 内化 中枢神经系统 突触后膜 离子型谷氨酸受体
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GluR2缺失的AMPARs在突触可塑性机制中的研究进展 被引量:4
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作者 魏显招 王雪琦 《第二军医大学学报》 CAS CSCD 北大核心 2009年第4期437-441,共5页
α-氨基-3-羟基-5-甲基-4-异唑-丙酸(AMPARs)是调节快速突触传递的兴奋性谷氨酸受体,是由GluR1、GluR2、GluR3和GluR4四种亚基选择性组装构成同源或异源四聚物。GluR2亚基对AMPARs的特性有重要影响,含GluR2亚基的AMPARs对Ca2+不通透,中... α-氨基-3-羟基-5-甲基-4-异唑-丙酸(AMPARs)是调节快速突触传递的兴奋性谷氨酸受体,是由GluR1、GluR2、GluR3和GluR4四种亚基选择性组装构成同源或异源四聚物。GluR2亚基对AMPARs的特性有重要影响,含GluR2亚基的AMPARs对Ca2+不通透,中枢神经系统中大多数AMPARs为此类;不含GluR2亚基的AMPARs对Ca2+有较好的通透性,这类AMPARs在限定的神经元或特定的生理或病理条件下表达。近年来的研究发现,GluR2缺失的AMPARs对突触功能、突触可塑性、神经局部环路传导等有特殊的作用。本文对GluR2缺失的AMPARs及其对突触功能和可塑性的作用作一综述。 展开更多
关键词 ampa受体 GluR2亚基 突触可塑性
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