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The abuse of anesthetic propofol: associated with cognitive impairment

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Science China(Life Sciences) 2018年第11期61卷 1428-1431页

作者： Weili Zhu Wen Zhang Jiali Li Zengbo Ding Yingjie Huang Lin Lu National Institute on Drug Dependence Peking University Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health Peking University

Propofol (2,6-diisopropylphenol)is a widely used intravenous anesthetic for the fast induction of anesthesia and rapid recovery from general anaesthesia.As a γ-aminobu-tyric acid(gaba)receptor agonist,propofol exerts... 详细信息

关键词： recovery effects fast gaba

The Effects of Glutamate and gaba (Gamma-Amino-Butyric-Acid) on Spontaneous Acetylcholine Release at the Neuromuscular Junction in Xenopus Laevis Embryo Cell Cultures

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Science China Chemistry 1993年第9期36卷 1110-1116页

作者：谢佐平汤云贵 Ron Stoop 毛健赵南明吕广能杨世若何湘萍汪海刘传缋 Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 PRC Department of Biological Sciences Columbia UniversityNew YorkNT10027USA Physiological Teaching Laboratory West China Medical University Chengdu 610044 PRC Institute of Toxicology and Pharmacology Military Medical Academy Beijing 100850 PRC

The miniature endplate currents (MEPC’s) were recorded at the neuromuscular junction of Xenopus laevis embryo neuron-muscle co-cultured cells. These MEPC’s were due to the spontaneous release of acetylcholine from the nerve terminal. After perfusion with glutamate (10 μmol/L), both frequency and amplitude of the MEPC’s increased. After washing away of glutamate, this effect persisted. We named this phenomena "Long-Term Facilitation".gaba (20 μmol/L) on the other hand had an inhibitory effect on both frequency and amplitude of the MEPC’s. After washing away of gaba, the MEPC frequency and amplitude increased. We named this effect "Post-Potentiation". Local perfusion experiments furthermore indicated that the effect of glutamate was restricted to the neuromuscular junction, the effect of gaba was restricted to the soma.

关键词： glutamate facilitation of MEPP gaba inhibition of MEPP.

Glyoxylate Reductase Isoform 1 is Localized in the Cytosol and Not Peroxisomes in Plant Cells

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Journal of Integrative Plant Biology 2012年第3期54卷 152-168页

作者： Steven L. K. Ching Satinder K. Gidda Amanda Rochon Owen R. van Cauwenberghe Barry J. Shelp Robert T. Mullen Department of Molecular and Cellular Biology University of Guelph Guelph Ontario N1G 2W1 Canada Department of Plant Agriculture University of Guelph Guelph Ontario N1G 2W1 Canada

Glyoxylate reductase （GLYR） is a key enzyme in plant metabolism which catalyzes the detoxification of both photorespiratory glyoxylate and succinic semialdehdye, an intermediate of the γ-aminobutyrate （gaba） pathway. Two isoforms of GLYR exist in plants, GLYR1 and GLYR2, and while GLYR2 is known to be localized in plastids, GLYR1 has been reported to be localized in either peroxisomes or the cytosol. Here, we reappraised the intracellular localization of GLYR1 in Arabidopsis thaliana L. Heynh （ecotype Lansberg erecta） using both transiently-transformed suspension cells and stably-transformed plants, in combination with fluorescence microscopy. The results indicate that GLYR1 is localized exclusively to the cytosol regardless of the species, tissue and/or cell type, or exposure of plants to environmental stresses that would increase flux through the gaba pathway. Moreover, the C-terminal tripeptide sequence of GLYR1, -SRE, despite its resemblance to a type 1 peroxisomal targeting signal, is not sufficient for targeting to peroxisomes. Collectively, these results define the cytosol as the intracellular location of GLYR1 and provide not only important insight to the metabolic roles of GLYR1 and the compartmentation of the gaba and photorespiratory pathways in plant cells, but also serve as a useful reference for future studies of proteins proposed to be localized to peroxisomes and/or the cytosol.

关键词： Arabidopsis gaba GLYR1 cytosol photobleaching peroxisome PTS stress tobacco BY-2.

Effects of dopamine D_(1) receptor blockade on the ERG b- and d-waves during blockade of ionotropic gaba receptors

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Eye and Vision 2016年第1期3卷 245-252页

作者： Elka Popova Momchil Kostov Petia Kupenova Department of Physiology Medical University of SofiaSofiaBulgaria

Background:Some data indicate that the dopaminergic and gabaergic systems interact in the vertebrate retina,but the type of interactions is not well understood.Methods:In this study we investigated the effect of dopamine D_(1) receptor blockade by 75μM SCH 23390 on the electroretinographic ON(b-wave)and OFF(d-wave)responses in intact frog eyecup preparations and in eyecups where the ionotropic gaba receptors were blocked by 50μM picrotoxin.Student’s t-test,One-way repeated measures ANOVA with Bonferroni post-hoc test and Two-way ANOVA were used for statistical evaluation of the data.Results:We found that SCH 23390 alone significantly enhanced the amplitude of the b-and d-waves without altering their latency.The effect developed rapidly and was fully expressed within 8-11 min after the blocker application.Picrotoxin alone also markedly enhanced the amplitude of the ERG ON and OFF responses and increased their latency significantly.The effect was fully expressed within 25-27 min after picrotoxin application and remained very stable in the next 20 min.The effects of SCH 23390 and picrotoxin are similar to that reported in our previous studies.When SCH 23390 was applied on the background of the fully developed picrotoxin effect,it diminished the amplitude of the b-and d-waves in comparison to the corresponding values obtained during application of picrotoxin alone.Conclusion:Our results demonstrate that the enhancing effect of D_(1) receptor blockade on the amplitude of the ERG b-and d-waves is not evident during the ionotropic gaba receptor blockade,indicating an interaction between these neurotransmitter systems in the frog retina.We propose that the inhibitory effect of endogenous dopamine mediated by D_(1) receptors on the ERG ON and OFF responses in the frog retina may be due to the dopamine-evoked gaba release.

关键词： Dopamine D_(1)receptors gaba Electroretinogram b-wave d-wave

EFFECTS OF CHOLECYSTOKININ OCTAPEPTIDE ON GENETICALLY DETERMINED SEIZURE SUSCEPTIBILITY

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中华医学杂志(英文版) 1992年第2期105卷 110-115页

作者：吴希如林彭新 100034 Beijing Division of Pediatric Neurology Department of Pediatrics First Teaching Hospital of Beijing Medical University 00034 Beijing Division of Pediatric Neurology Department of Pediatrics First Teaching Hospital of Beijing Medical University

Utilizing audiogenic seizure-prone P77PMCrats,the effects of cholecystokinin octapeptide（CCK-8）on genetic seizure susceptibility were studiedin vivo,in cerebral cortical synaptosomes,and incortical neuronal cell cultures.The results showed thatCCK-8 could decrease seizure susceptibility,and thatthe K-stimulated release of gaba in cerebral cortexsynaptosomes from seizure-prone animals was de-pressed.The presence of exogenous CCK-8(10M)together with elevated K（25mM）causes a higher in-creased magnitude in gaba release fromsynaptosomes （enhanced by 100%） and cell cultures（17 days in vitro,increased by 177%）derived from sei-zure-prone rats than the controls（increased by 42%,in synaptosomes;and 107% in cell cultures）.Thesepreliminary results raise the possibilitiy that thedevelopmental abnormalities in modulation effect ofCCK-8 on gaba release in central nervous systemmay play a role causing greater seizure susceptibilityin genetic seizure-prone rats.The analysis of the braintissue level and gene-expression of CCK-8 will be theimportant step of further investigation.

关键词： RAT CORTICAL-NEURONS CO-LOCALIZATION BRAIN gaba NEUROPEPTIDES PEPTIDES MICE COEXISTENCE HIPPOCAMPUS ANTAGONISM

Sex and Death:Identification of Feedback Neuromodulation Balancing Reproduction and Survival

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Neuroscience Bulletin 2020年第12期36卷 1429-1440页

作者： Can Gao Chao Guo Qionglin Peng Jie Cao Galit Shohat-Ophir Dong Liu Yufeng Pan The Key Laboratory of Developmental Genes and Human Disease School of Life Science and TechnologySoutheast UniversityNanjing 210096China School of Life Sciences Nantong UniversityNantong 226019China The Mina&Everard Goodman Faculty of Life Sciences and Susan Gonda Multidisciplinary Brain Research Center Bar-Ilan UniversityRamat-Gan 5290002Israel Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226019China

Some semelparous organisms in nature mate as many times as they can in a single reproductive episode before death,while most iteroparous species including humans avoid such suicidal reproductive behavior.Animals naturally pursue more sex and the possible fatal consequence of excessive sex must be orchestrated by negative feedback signals in iteroparous species,yet very little is known about the regulatory mechanisms.Here we used Drosophila male sexual behavior as a model system to study how excessive sex may kill males and how the nervous system reacts to prevent death by sex.We found that continuous sexual activity by activating the fruitlessexpressing neurons induced a fixed multi-step behavioral pattern ending with male death.We further found negative feedback in the fly brain to prevent suicidal sexual behavior by expression changes of the neurotransmitters acetylcholine and gamma-aminobutyric acid,and neuropeptide F.These findings are crucial to understand the molecular underpinnings of how different organisms choose reproductive strategies and balance reproduction and survival.

关键词： Drosophila Reproduction Survival NPF gaba Acetylcholine

稳定表达人源gaba_(A)R-CHO细胞株的建立

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中国生物工程杂志 2022年第3期42卷 38-46页

作者：张毅王陈石晶晶陈学军张瑞华靳倩石童李丽琴国民核生化灾害防护国家重点实验室北京102205

目的:构建α_(1)亚基诱导表达、β_(2)和γ_(2L)亚基稳定表达的人源α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO(Chinese hamster ovary)细胞株。方法:从人cDNA文库中扩增α_(1)、β_(2)、γ_(2L)亚基编码基因,分别构建亚基表达载体;将三个亚基... 详细信息

目的:构建α_(1)亚基诱导表达、β_(2)和γ_(2L)亚基稳定表达的人源α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO(Chinese hamster ovary)细胞株。方法:从人cDNA文库中扩增α_(1)、β_(2)、γ_(2L)亚基编码基因,分别构建亚基表达载体;将三个亚基表达载体共转染CHO-K1细胞,通过抗性筛选、膜电位检测法进行稳定表达克隆筛选;通过qPCR、Western blot对亚基表达进行鉴定;以激动剂gaba、阳性变构调节剂地西泮(diazepam,Dia)、拮抗剂荷包牡丹碱(bicuculine)为工具药,采用全细胞膜片钳方法及膜电位检测法对稳定表达细胞的药理学功能进行鉴定。结果:经克隆筛选获得表达量较高的α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO并对其亚基表达鉴定,结果显示该细胞稳定表达α_(1)、β_(2)、γ_(2L)亚基,构建的α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO细胞仅在加入四环素(tetracyclin)诱导的情况下表达α_(1)亚基并与β_(2)、γ_(2L)组装成具有功能活性的α_(1)β_(2)γ_(2L)-gaba_(A)R;对其进行全细胞膜片钳检测研究发现,gaba可对其产生激动效应,引起α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO细胞产生氯离子通道特征性电流变化,Dia可剂量依赖性地增强gaba对α_(1)β_(2)γ_(2L)-gaba_(A)R的激动效应;在膜电位检测研究中,获得gaba激动效应EC_(50)为(177.72±15.92)nmol/L,Dia变构效应EC_(50)为(3.63±0.52)μmol/L,拮抗剂Bicuculine拮抗效应IC50为(538.83±29.55)nmol/L。结论:通过采用诱导表达策略,成功构建了α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO稳定表达细胞株,该细胞株具有对激动剂、阳性变构剂、拮抗剂特异性检测的药理学功能。

关键词： α_(1)β_(2)γ_(2L)-gaba_(A)R-CHO 诱导表达膜电位检测 gaba 地西泮

gaba旁路在阪崎克罗诺杆菌耐干燥胁迫中的作用

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现代食品科技 2023年第2期39卷 297-302页

作者：黎丽曹怡芳张艳肖性龙华南理工大学食品科学与工程学院广东广州510640

阪崎克罗诺杆菌是婴幼儿配方奶粉(Powdered Infant Formula,PIF)中常见的食源性致病菌,γ-氨基丁酸(γ-Aminobutyric Acid,gaba)是一种广泛存在于各种生物体内的非蛋白氨基酸,而gabT控制的氨基丁酸转氨酶是gaba代谢旁路的关键酶。该研... 详细信息

阪崎克罗诺杆菌是婴幼儿配方奶粉(Powdered Infant Formula,PIF)中常见的食源性致病菌,γ-氨基丁酸(γ-Aminobutyric Acid,gaba)是一种广泛存在于各种生物体内的非蛋白氨基酸,而gabT控制的氨基丁酸转氨酶是gaba代谢旁路的关键酶。该研究通过构建阪崎克罗诺杆菌ATCC 29544 gabT基因敲除菌株(ΔgabT),探讨gabT控制的gaba(γ-氨基丁酸)代谢旁路对阪崎克罗诺杆菌抵抗干燥的作用。结果表明,ΔgabT在干燥胁迫下处理一周后存活率可达到28.64%显著高于野生型菌株(WT)的存活率1.57%。此外,gaba在ΔgabT中累积量高于WT,与存活率结果呈正相关,表明gaba累积能帮助阪崎克罗诺杆菌抵御干燥胁迫。扫描电子显微镜检测结果也显示ΔgabT菌株具有较完整的细胞形态,进一步验证了gaba积累有助于阪崎克罗诺杆菌在干燥环境胁迫下的生存。该研究为阪崎克罗诺杆菌中基于gaba旁路的靶向调控奠定了基础,为阪崎克罗诺杆菌防控提供新思路。

关键词：阪崎克罗诺杆菌 gabT gaba 耐干燥

Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第11期9卷 903-915页

作者： Hai-ju ZHANG Ruo-peng SUN Ge-fei LEI Lu YANG Chun-xi LIU Department of Pediatrics Renmin Hospital of Wuhan University Wuhan 430060 China Department of Pediatrics Qilu Hospital of Shandong University Jinan 250012 China Key Laboratory of Cardiovascular Remodeling and Function Research Qilu Hospital of Shandong University Jinan 250012 China

Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods: Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature gabaergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (gabaA) receptors and mitogen-activated protein kinase/extracellular sig- nal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of gabaA receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a gabaergic mechanism.

关键词： COX-2 神经发生小胶质细胞 gaba 细胞分裂