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SOX2/DRD2 signaling pathway facilitates astrocytic dedifferentiation in cerebral ischemic mice
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作者 YI Xuyang KANG Enming +4 位作者 WANG Yanjin ZHANG Kun LIN Wei WU Shengxi WANG Yazhou 《神经解剖学杂志》 CAS CSCD 北大核心 2024年第3期277-286,共10页
Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mic... Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke. 展开更多
关键词 cerebral ischemia ASTROCYTE DEDIFFERENTIATION SOX2 dopamine d2 receptor(drd2) mouse
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Effects of Ovariectomy and 17β-Estradiol Replacement on the Activity of Dopamine D2 Receptors in the Selection of Macronutrients Carbohydrates, Lipids and Proteins in Females Rats
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作者 Brahima Bamba Seydou Silué +1 位作者 Tiémélé Eugène Atayi Antoine Némé Tako 《Journal of Biosciences and Medicines》 CAS 2023年第5期76-110,共35页
17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body wei... 17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight. 展开更多
关键词 17Β-ESTRADIOL d2 receptors BROMOCRIPTINE SULPIRIDE Carbohydrates LIPIDS PROTEINS Body Weight Menopause Obesity
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Modeling of Dopamine D2 Receptor and its Agonist DOCK Analyses
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作者 朱七庆 郭宗儒 《Journal of Chinese Pharmaceutical Sciences》 CAS 1998年第3期3-8,共6页
A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis exp... A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis experience, the binding pocket, including nine amino acid residues beside indispensable Asp86, Ser141 and Ser144 residues, was defined. In order to testify the 3D structure of dopamine D2 receptor and specially test the binding sites, two sets of D2 receptor agonists (one was rigid and the other flexible) were selected for docking. A good result of correlation between logIC 50 and binding energy E b indicates that the predicted model is reliable for the investigation of the receptor ligand interaction and design of new active molecules. 展开更多
关键词 dopamine d2 receptor 3D structure prediction DOCK
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Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight 被引量:1
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作者 Abdoulaye Ba Seydou Silué +2 位作者 Brahima Bamba Lociné Bamba Serge-Vastien Gahié 《Journal of Behavioral and Brain Science》 2018年第1期1-25,共25页
Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or ... Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity. 展开更多
关键词 17β-Estradiol dopamine d2 receptors BROMOCRIPTINE SULPIRIDE Water SUCROSE ALCOHOL Intakes Obesity
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Down-regulation of dopamine D2 receptor associates with impaired reversal learning induced by morphine withdrawal
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作者 LI Fei HE Li +1 位作者 LI Jin Jennifer L WHISTLER 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2018年第9期717-717,共1页
OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study e... OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study examined the impact of morphine withdrawal on reversal learning.METHODS Reversal learning was tested in a four-choices digging task.Some brain tissues were harvested 2 h after the behavioral experiment for the further measurement.RESULTS We found that after long-term abstinence for a month from chronic morphine exposure,mice exhibited a profound reversal learning deficit.We further found that dopamine D2 receptor(D2R)system in the frontal-striatal circuit is significantly down-regulated,at both receptor and downstream signals levels.Subsequent pharmacological experiments demonstrated that aripiprazole,a D2R partial agonist,prevented the D2R downregulation and rescued the reversal learning deficit.CONCLUSION Together,our findings provide valuable insights into the causal relationship between D2R system in the frontal-striatal circuit and the cognitive inflexibility caused by abused drugs and offer a promising possibility of an effective therapeutic intervention for drug addictions. 展开更多
关键词 REVERSAL learning dopamine d2 receptor MORPHINE cognitive INFLEXIBILITY
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Effects of 17<i>β</i>-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight
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作者 Seydou Silué Abdoulaye Bâ 《Journal of Biosciences and Medicines》 2019年第11期36-55,共20页
Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation... Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation on dopamine D2 receptors, using bromocriptine mesylate (BR) and sulpiride (SUL) as selective central dopamine-D2 receptors agonist and antagonist respectively. We studied the E2-dopamine D2 receptors interferences in a 10-day thiamine-deficient female rats for which consumptions of water, sugar, alcohol and food were daily-recorded and their consequences on body weights assessed. Our results showed that the volume of water daily ingested doubled in thiamine-deficient female rats (OXT), while sugar and alcohol consumptions collapsed with decreased weight and food consumption. On the one hand, thiamine potentiated D2/BR activity (bromocriptine-activated D2 receptors) to induce sugar intake and inhibited the same D2/BR receptors to induce water intake. On the other hand, thiamine promoted D2/SUL receptors (sulpiride-inhibited D2 receptors) for enhanced alcohol intake, increased food consumption and weight gain. Taking together, thiamine modulated the actions of 17β-estradiol on both D2/BR and D2/SUL receptors activities. 展开更多
关键词 THIAMINE Deficiency 17β-Estradiol d2 receptors SUCROSE ALCOHOL Intakes Body Weight
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CYP2D6和DRD2基因多态性及其交互作用与阿立哌唑疗效的关联研究 被引量:3
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作者 闫盼 宋明芬 +4 位作者 李欣 王晟东 王姝琪 李静 施剑飞 《浙江医学》 CAS 2019年第22期2369-2373,共5页
目的探讨细胞色素P4502D6(CYP2D6)和多巴胺D2受体(DRD2)基因多态性及其交互作用与阿立哌唑治疗精神分裂症临床疗效的关联。方法选取120例接受单一阿立哌唑治疗4周的精神分裂症住院患者为研究对象,采用4周末阳性与阴性症状量表(PANSS)减... 目的探讨细胞色素P4502D6(CYP2D6)和多巴胺D2受体(DRD2)基因多态性及其交互作用与阿立哌唑治疗精神分裂症临床疗效的关联。方法选取120例接受单一阿立哌唑治疗4周的精神分裂症住院患者为研究对象,采用4周末阳性与阴性症状量表(PANSS)减分率评定药物疗效,其中有效(≥50%)组69例,无效(<50%)组51例。采用多重高温连接酶检测反应技术检测CYP2D6(rs1065852、rs1135840)和DRD2(rs1799732、rs1800497)基因多态性;采用多因子降维法(MDR)分析基因-基因交互作用,多因素logistic逐步回归分析估计CYP2D6和DRD2基因多态性及其交互作用的效应。结果有效组与无效组rs1065852、rs1799732、rs1800497位点等位基因及基因型频率分布比较,差异均有统计学意义(均P<0.05);rs1135840位点等位基因及基因型频率分布比较,差异均无统计学意义(均P>0.05)。rs1065852、rs1799732、rs1800497位点多态性之间存在交互作用。rs1065852、rs1799732、rs1800497多态性及其交互作用均可影响阿立哌唑治疗精神分裂症的疗效,其OR值(95%CI)分别为3.269(1.124~9.510)、0.188(0.048~0.738)、3.314(1.336~8.218)、3.395(1.047~11.001)。结论CYP2D6(rs1065852)和DRD2(rs1799732、rs1800497)基因多态性与阿立哌唑治疗精神分裂症疗效相关,其对阿立哌唑疗效的影响存在正交互作用。 展开更多
关键词 精神分裂症 阿立哌唑 CYP2D6 drd2 基因多态性 基因-基因交互作用 临床疗效
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Variation in the <i>DRD2</i>gene affects impulsivity in intertemporal choice 被引量:1
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作者 Yoshiya Kawamura Taiki Takahashi +5 位作者 Xiaoxi Liu Nao Nishida Yoshihiro Noda Akane Yoshikawa Tadashi Umekage Tsukasa Sasaki 《Open Journal of Psychiatry》 2013年第1期26-31,共6页
Introduction: Impulsivity in intertemporal choice has been operationalized as “delay discounting,” referring to the preference for a sooner, smaller reward in neuroeconomics. It is reportedly associated with the dop... Introduction: Impulsivity in intertemporal choice has been operationalized as “delay discounting,” referring to the preference for a sooner, smaller reward in neuroeconomics. It is reportedly associated with the dopaminergic systems. Dopamine receptor D2 (DRD2) is the D2 subtype of the dopamine receptor of the G-protein coupled receptor family. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in DRD2 gene on delay discounting. Methods: The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed the Kirby’s monetary choice questionnaire (MCQ) for delayed gain and donated a whole blood sample. Two SNPs (C957T (rs6277) and TaqI A (rs1800497)) in DRD2 were genotyped by using the DigiTag2 assay. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k). Results: The SNP C957T showed a significant association;participants with more minor alleles (T) were more impulsive in intertemporal choice for delayed gain (multiplicity-corrected P = 0.041 with a small effect size). Conclusion: The variation in the DRD2 gene is associated with impulsive decision-making. This is the first study to demonstrate an association between DRD2 and impulsivity in intertemporal choice with a multiplicity-corrected significance. 展开更多
关键词 dopamine receptor d2 (drd2) IMPULSIVITY NEUROECONOMICS Single NUCLEOTIDE Polymorphism (SNP) Time-Discount Rate
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Correlation between DRD2 Gene Polymorphism and Early Egg Production Performance of Libo Yaoshan Chicken
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作者 Zhu Lili Li Dongguang +2 位作者 Xu Longxin Han Xue Wu Gemin 《Animal Husbandry and Feed Science》 CAS 2015年第4期208-211,共4页
To improve egg production performance of local chicken breed in Guizhou Province, Libo Yaoshan chicken, with dopamine receptor 2 ( DRD2 ) as one of the candidate genes, we detected its genetic variation in 196 Libe ... To improve egg production performance of local chicken breed in Guizhou Province, Libo Yaoshan chicken, with dopamine receptor 2 ( DRD2 ) as one of the candidate genes, we detected its genetic variation in 196 Libe Yaoshan hens using PCR-SSCP (single-strand conformation polymorphism) and sequencing method, and analyzed the correlation between genetic variation and egg production traits. The results showed that TT and TG genotypes in mRNA SNlX)62 (C→T) loci of the DRD2 gene had extremely significant difference in egg production at 38 weeks age (P 〈0.01 ), and significant difference in egg weight at 300 days age (P 〈0.05 ). The single nucleotide polymorphisms (SNPs) mutation induced synonymous mutation of the 312th amino acids (leucine) in DRD2 protein, from L (CTG) to L (TI'G). The mRNA SNP962 (C→T) loci had a larger genetic effect on egg production at 38 weeks age, and could be used as a molecular marker in early breeding of Libo Yaoshan chicken. 展开更多
关键词 dopamine receptor 2 drd2 gene Gene polymorphism Libo Yaoshan chicken Early egg production performance PCR-SSCP
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DRD2启动子低甲基化通过ERK通路调控乳腺癌细胞增殖
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作者 钟明 袁浩 +5 位作者 钱丰源 朱红波 伍雯 蒋晓飞 游庆华 李永平 《复旦学报(医学版)》 CAS CSCD 北大核心 2022年第5期704-712,719,共10页
目的研究肿瘤干细胞标志物多巴胺受体D2(dopamine receptor D2,DRD2)对乳腺癌细胞增殖的影响。方法采用850K芯片对乳腺癌组织进行检测,并分析DRD2甲基化状态。采用基因筛选、基因敲除和甲基化抑制等技术和方法,进行体外和体内实验,筛选... 目的研究肿瘤干细胞标志物多巴胺受体D2(dopamine receptor D2,DRD2)对乳腺癌细胞增殖的影响。方法采用850K芯片对乳腺癌组织进行检测,并分析DRD2甲基化状态。采用基因筛选、基因敲除和甲基化抑制等技术和方法,进行体外和体内实验,筛选和验证可能存在的分子信号通路。结果DRD2启动子区在乳腺癌组织中相较于正常组织表现为低甲基化。上调DRD2的表达后,乳腺癌细胞增殖增强,而下调DRD2的表达,乳腺癌细胞增殖显著降低。裸鼠实验发现,过表达DRD2可促进肿瘤生长和Ki67、CD31表达,下调DRD2可抑制肿瘤生长。体内外实验表明,细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)的表达受DRD2表达水平的影响,提示DRD2通过ERK信号通路发挥作用。甲基化抑制剂5-aza-2-脱氧胞苷(5-aza-2-deoxycytidine,5-AzadC)在小鼠体内部分逆转了DRD2表达的下调,失去了对肿瘤细胞增殖的抑制作用,提示抑制DRD2甲基化促进了肿瘤的发展。结论乳腺癌中DRD2启动子区发生低甲基化。DRD2通过ERK通路在乳腺癌细胞的增殖和迁移中发挥作用。 展开更多
关键词 乳腺癌 多巴胺受体d2(drd2) 甲基化 细胞外调节蛋白激酶(ERK)通路
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DRD2基因多态性与奥氮平治疗早发精神分裂症疗效的相关性研究 被引量:3
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作者 林春燕 李志芸 +1 位作者 黎顺成 刘向来 《精神医学杂志》 2022年第1期64-68,共5页
目的分析多巴胺受体D_(2)(DRD2)基因多态性与奥氮平治疗早发精神分裂症(EOS)疗效的关系。方法选取接受奥氮平单药治疗的214例EOS患者,治疗前采用限制性片段长度多态性(PCR-RFLP)法测定DRD2(rs6276)基因型,并于治疗前及治疗后第8周末进... 目的分析多巴胺受体D_(2)(DRD2)基因多态性与奥氮平治疗早发精神分裂症(EOS)疗效的关系。方法选取接受奥氮平单药治疗的214例EOS患者,治疗前采用限制性片段长度多态性(PCR-RFLP)法测定DRD2(rs6276)基因型,并于治疗前及治疗后第8周末进行阳性与阴性症状量表(PANSS)评分,评定疗效;比较不同DRD2(rs6276)基因多态性患者治疗前后PANSS评分、疗效、不良反应发生率。结果治疗后患者PANSS总分及阳性症状、阴性症状、一般精神病理评分均较治疗前下降(P<0.05)。治疗总有效率63.08%,按奥氮平治疗疗效分组,两组DRD2基因rs6276位点等位基因频率符合Hardy-Weinberg平衡定律(P>0.05),有效组中DRD2基因rs6276位点TT基因型、T等位基因频率高于无效组(P<0.05)。不同DRD2(rs6276)基因多态性患者不良反应发生率比较差异均无统计学意义(P>0.05)。回归分析结果显示,DRD2(rs6276)基因型、DRD2(rs6276)等位基因是奥氮平疗效的影响因素(P<0.05)。结论EOS患者中携带DRD2(rs6276)T等位基因、TT基因型患者奥氮平治疗效果更佳,且DRD2(rs6276)基因多态性与不良反应无明显关联。 展开更多
关键词 早发精神分裂症 多巴胺受体D_(2) 奥氮平 疗效
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DRD2(-141C Ins/Del)多态性与利培酮所致精神分裂症患者高泌乳素血症的相关性分析 被引量:6
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作者 邬俊福 张运才 彭红波 《实用药物与临床》 CAS 2019年第4期374-377,共4页
目的探讨垂体多巴胺2受体拮抗(DRD2)基因启动子区域-141C Ins/Del基因多态性与利培酮治疗导致的精神分裂症患者高泌乳素血症之间的相关性。方法按照美国精神病学会制定的精神障碍诊断与统计手册诊断标准,收集我院148例精神科汉族精神分... 目的探讨垂体多巴胺2受体拮抗(DRD2)基因启动子区域-141C Ins/Del基因多态性与利培酮治疗导致的精神分裂症患者高泌乳素血症之间的相关性。方法按照美国精神病学会制定的精神障碍诊断与统计手册诊断标准,收集我院148例精神科汉族精神分裂症患者纳入研究组,另选取我院130例汉族体检健康者为对照组。两组均接受同一批次利培酮药物治疗,治疗前与治疗6周后抽取外周血,采用微粒酶免疫分析法对用药前后的泌乳素含量进行测定,采用聚合酶链式反应-限制性片段长度多肽分析(PCR-RELP)技术对外周血提取ERD2基因多态性位点(-141C Ins/Del)进行基因分型,利用吻合度检验检测Hardy-Weinberg平衡。结果 Hardy-weinberg遗传平衡吻合度检验显示,研究组与对照组各基因型分布符合与等位基因频率上差异均无统计学意义(P>0.05),符合遗传平衡差异;D2R2(-141C Ins/Del)基因多态性在性别、年龄、婚姻史、家族史、起病形式方面差异无统计学意义(P>0.05),在有无精神创伤史方面差异有统计学意义(P<0.05);研究组患者接受利培酮治疗6周后,血清泌乳素水平升高(P<0.05);Del携带者升高幅度显著低于Ins携带者,且Del/Del型泌乳素升高幅度最低(P<0.05)。结论 DRD2基因-141C Ins/Del多态性有望成为预测利培酮治疗精神分裂症患者所致高泌乳素血症的潜在生物学标志。 展开更多
关键词 垂体多巴胺2受体拮抗 利培酮 精神分裂症 高泌乳素血症
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Paired related homeobox 1 transactivates dopamine D2 receptor to maintain propagation and tumorigenicity of glioma-initiating cells 被引量:5
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作者 Yamu Li Wen Wang +11 位作者 Fangyu Wang Qiushuang Wu Wei Li Xiaoling Zhong Kuan Tian Tao Zeng Liang Gao Ying Liu Shu Li Xiaobing Jiang Guangwei Du Yan Zhou 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2017年第4期302-314,共13页
GUoblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils (GICs/GSCs) may be responsibl... GUoblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 (PRRX1), a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation. Further, PRRX1 is overrepresented in gUoma samples and labels GlCs. Gtioma celts and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model. The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor (DRD2). PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GICs. Blockage of the DRD2 signaling hampers GIC self-renewal, whereas its overexpression restores the propagating and tumorigenic potential of PRRXl-depleted GlCs. Finally, PRRX1 potentiates GICs via DRD2-mediated extracetlutar signal-related kinase (ERK) and AKT activation. Thus, our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GICs is a promising strategy for treating GBMs. 展开更多
关键词 paired related homeobox 1 dopamine d2 receptor glioma-initiating cells glioblastoma
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Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain 被引量:3
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作者 Shi-Hao Gao Yong Tao +3 位作者 Yang Zhu Hao Huang Lin-Lin Shen Chang-Yue Gao 《Neuroscience Bulletin》 SCIE CAS CSCD 2022年第9期1041-1056,共16页
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,whic... Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain. 展开更多
关键词 Inflammatory pain Lateral entorhinal cortex Neuronal hyperexcitability dopamine d2 receptor HCN current
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Dopamine D2 Receptor-Mediated Modulation of Rat Retinal Ganglion Cell Excitability 被引量:2
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作者 Ning Yin Yu-Long Yang +5 位作者 Shuo Cheng Hong-Ning Wang Xin Hu Yanying Miao Fang Li Zhongfeng Wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2020年第3期230-242,共13页
Ganglion cells(RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 ... Ganglion cells(RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 receptor agonist quinpirole inhibited outward K^+ currents, which were mainly mediated by glybenclamide-and 4-aminopyridine-sensitive channels, but not the tetraethylammonium-sensitive channel. In addition,quinpirole selectively enhanced Nav1.6 voltage-gated Na^+ currents. The intracellular c AMP/protein kinase A,Ca^2+/calmodulin-dependent protein kinase Ⅱ, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were responsible for the effects of quinpirole on K^+ and Na^+ currents, while phospholipase C/protein kinase C signaling was not involved. Under current-clamp conditions, the number of action potentials evoked by positive current injection was increased by quinpirole. Our results suggest that D2 receptor activation increases RGC excitability by suppressing outward K+currents and enhancing Nav1.6 currents, which may affect retinal visual information processing. 展开更多
关键词 Retinal GANGLION cell dopamine d2 receptor Outward K^+current Nav1.6 VOLTAGE-GATED Na^+current EXCITABILITY
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The role of dopamine D2 receptors in the amygdala in metabolic and behavioral responses to stress in male Swiss-Webster mice 被引量:2
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作者 Maryam Hassantash Hedayat Sahraei +2 位作者 Zahra Bahari Gholam Hossein Meflahi Roshanak Vesali 《Frontiers in Biology》 CAS CSCD 2017年第4期298-310,共13页
OBJECTIVE: The D2 dopamine receptor is found in different parts of the amygdala. However, its contribution to stress is unknown. Thus, in the present study, we examined the effects of excitation and inhibition of D2 ... OBJECTIVE: The D2 dopamine receptor is found in different parts of the amygdala. However, its contribution to stress is unknown. Thus, in the present study, we examined the effects of excitation and inhibition of D2 dopamine receptors in the amygdala on the metabolic and hormonal changes in response to stress. METHODS: Bilateral amygdala cannulation was carried out in Swiss-Webster mice (n = 7). On recovery, different doses of the dopamine D2 receptor antagonist, sulpiride (1, 5 and 10μg/mouse) or the dopamine D2 receptor agonist, bromocriptine (1, 5 and 10μg/mouse) were injected into the amygdala. The animals were then placed in stress apparatus (communication box) where they received an electric shock (10 mV voltage, 10 Hz frequency and 60 s duration) after 30 rain. The animal's activities were recorded for 10 min before and 10 min after the stress induction. Locomotion, rearing and freezing were investigated. Metabolic changes, such as food and water intake and anorexia, were studied. RESULTS: The results show that stress increased the concentration of plasma corticosterone, which was followed by a decrease in locomotion and rearing and an increase in freezing behavior. Furthermore, both weight and water and food intake were reduced. Administration of bromocriptine led to a reduction of corticosterone at doses of 1 and 5 ~tg/mouse and an increase of corticosterone at 10 ~tg/mouse. Additionally, lower doses ofbromocriptine (1 and 5 ~tg/mouse) caused an increase in locomotion and rearing and a decrease in freezing behavior. Similar results were observed with sulpiride injection. CONCLUSION: D2 dopamine receptors can play a major role in the amygdala in stress. Both an agonist and an antagonist of the D2 receptor attenuate the metabolic and hormonal changes observed in response to stress 展开更多
关键词 AMYGDALA ANOREXIA BROMOCRIPTINE CORTICOSTERONE d2 dopamine recepetor SULPIRIDE
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β内啡肽、环氧合酶-2、多巴胺受体D2在右向左分流合并有先兆偏头痛患者血清中的表达及其与焦虑状况的关联性
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作者 郑瑶 王宝月 +2 位作者 贾琳楠 曲海丽 孙晖 《中国医药导报》 CAS 2024年第7期101-104,109,共5页
目的 研究β内啡肽(β-EP)、环氧化酶-2(COX-2)、多巴胺受体D2(DRD2)在右向左分流(RLS)合并有先兆偏头痛患者血清中的表达及其与焦虑状况的关联性。方法 选取2022年7月至2023年7月吉林省一汽总医院收治的214例检查存在RLS的有先兆偏头... 目的 研究β内啡肽(β-EP)、环氧化酶-2(COX-2)、多巴胺受体D2(DRD2)在右向左分流(RLS)合并有先兆偏头痛患者血清中的表达及其与焦虑状况的关联性。方法 选取2022年7月至2023年7月吉林省一汽总医院收治的214例检查存在RLS的有先兆偏头痛患者,记作RLS偏头痛组,50例检查无RLS的有先兆偏头痛患者作为对照组,比较两组血清β-EP、COX-2、DRD2水平及焦虑自评量表(SAS)评分。另将RLS偏头痛组患者根据检查结果分为少、中、大量RLS偏头痛组(78例),分别为90、46、78例,比较三组血清β-EP、COX-2、DRD2水平及SAS评分。采用Spearman相关系数分析RLS偏头痛组患者血清β-EP、COX-2、DRD2水平与RLS分级、SAS评分的关系。结果 RLS偏头痛组血清β-EP、DRD2水平均低于对照组,COX-2水平及SAS评分高于对照组,差异有统计学意义(P<0.05)。中、大量RLS偏头痛组血清β-EP、DRD2水平低于少量RLS偏头痛组,大量RLS偏头痛组低于中量RLS偏头痛组,差异有统计学意义(P<0.05)。中、大量RLS偏头痛组血清COX-2水平、SAS评分高于少量RLS偏头痛组,大量RLS偏头痛组高于中量RLS偏头痛组,差异有统计学意义(P<0.05)。相关性分析结果显示,RLS偏头痛组患者血清β-EP、DRD2水平与RLS分级、SAS评分呈负相关(rs<0,P<0.05),血清COX-2水平与RLS分级、SAS评分呈正相关(rs>0,P<0.05)。结论 随着RLS合并有先兆偏头痛患者RLS分级的升高,其血清β-EP、DRD2表达降低,COX-2表达升高,且三者均与患者的焦虑状态密切相关。 展开更多
关键词 有先兆偏头痛 右向左分流 Β内啡肽 环氧合酶-2 多巴胺受体d2 焦虑
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Effect of total isoflavones from pueraria lobata on the expressions of preproenkephalin, prodynorphin and D2 dopamine receptor mRNA in PC12 cells induced by MPP^+
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作者 Miaoxian Dong Chengchong Li +3 位作者 Yutao Gen Chun Zhang Xiaoming Li Yingcai Niu 《The Chinese-German Journal of Clinical Oncology》 CAS 2010年第1期48-52,共5页
Objective: The aim of the study was to observe the effect of total isoflavones from pueraria Iobata (TIP) on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson's disea... Objective: The aim of the study was to observe the effect of total isoflavones from pueraria Iobata (TIP) on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson's disease (PD) model cells induced by 1-methyl-4-phenylpyridinium ion (MPP^+). Methods: TIP was dissolved in 0.1 M NaOH and added to the culture medium at a final concentrations of 50 mg/L, 100 mg/L and 200 mg/L. Some cells (control) were exposed to 0.001 M NaOH. TIP was added to PC12 cells 30 min prior to the administration of MPP^+. TIP and MPP^+ remained in the culture medium for 96 h. D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions were assayed by real-time quantitative reverse transcription-PCR. Results: The D2 dopamine receptor mRNA and preproenkephalin mRNA expressions were up-regulated in MPP^+ group compared with the control group, and prodynorphin mRNA expression was down-regulated in that. The D2 dopamine receptor mRNA expression being down-regulated and prodynorphin mRNA expression being up-regulated in TIP group compared with the MPP^+ group. And there was no effect of TIP on preproenkephalin gene expression in PC12 cells induced by MPP^+. Conclusion: The results suggest that TIP down-regulates the D2 dopamine receptor mRNA expression, up-regulates prodynorphin mRNA expression and not affects preproenkephalin gene expression in PC12 cells induced by MPP^+. 展开更多
关键词 Parkinson's disease (PD) total isoflavones from pueraria Iobata (TIP) PREPROENKEPHALIN d2 dopamine receptor PRODYNORPHIN 1-methyl-4-phenylpyddinium ion (MPP^+)
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创伤后应激障碍致病基因(DRD2)研究进展
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作者 康延海 郭敏 +4 位作者 邓立群 盛莉 蔡俊宏 陈峰 郭骏成 《中国热带医学》 CAS 2013年第8期1039-1042,共4页
创伤后应激障碍(PTSD)是个体在突然遭遇强烈的精神应激后出现的延迟发生而又较持久的应激障碍。本文就多巴胺D2基因(DRD2),多巴胺D2受体及多巴胺系统与PTSD疾病发生及其相关特性方面进行了阐述。
关键词 创伤后应激障碍 drd2基因 多巴胺d2受体 综述
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Effects of Ningdong granule on DA,DRD2,and HVA in a rat model of Tourette's syndrome 被引量:2
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作者 吕红 林海燕 +3 位作者 赵辉 李安源 林莺 姚冰 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2012年第2期283-288,共6页
OBJECTIVE:Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome.METHODS:Sixty-four rats were randomly assigned to a control group and three experimental groups,res... OBJECTIVE:Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome.METHODS:Sixty-four rats were randomly assigned to a control group and three experimental groups,respectively.Rat models of Tourette's syndrome were established via intraperitoneal injection of apomorphine(Apo).The rats in the experimental groups were subsequently intragastrically injected with haloperidol at 10 mg/kg(haloperidol group),Ningdong granule at 370 mg/kg(NDG group),and normal saline(0.9%) at 10 mL/kg(Apo group),respectively.Rat behaviors were observed and recorded on a daily basis.After 12 w,all rats were sacrificed,and sera and striatal tissues were harvested.Homovanillic acid levels in sera,as well as dopamine and dopamine D2 receptor mRNA expression in the striatum,were measured to determine possible mechanisms of Ningdong granule on the dopamine system in a rat model of Tourette's syndrome.RESULTS:Following intervention,stereotype actions of the Tourette's syndrome rats were significantly inhibited in the haloperidol and NDG groups,respectively(P<0.01).Homovanillic levels were significantly greater in the haloperidol and NDG groups,respectively(P<0.05).In addition,dopamine levels were significantly less in the NDG group(P<0.01),and DRD2 mRNA expression was significantly reduced in the haloperidol and NDG groups,respectively(P<0.05).CONCLUSION:Results demonstrated that Ningdong granule effectively inhibited stereotype actions and Tourette's syndrome symptoms by promoting dopamine metabolism,reducing dopamine levels in the striatum,increasing homovanillic acid content in sera,and reducing mRNA expression of DRD2 in the striatum. 展开更多
关键词 Ningdong granule Tourette's syndrome Rat models dopamine Homovanillic acid dopamine d2 receptor
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