Danio rerio

Danio rerio
  • 文章类型: Journal Article
    糖皮质激素(GC)对动物行为具有广泛的影响。最近提出的效果涉及确定个体差异的结构,这就是个体的行为特征如何相互变化,形成所谓的行为综合症。由于GCs可以以多种方式发挥其作用,例如,通过快速的非基因组效应或通过激活作为转录因子的类固醇受体家族的两个高度同源的成员,目前尚不清楚GC对行为综合征的调制是如何发生的。我们利用了编码GC受体(Gr)的基因中具有移码突变的斑马鱼系,来调查这个问题。我们发现缺乏Gr改变了突变系中几种行为特征的平均得分,确定降低的胆量,增加活动和社交能力。严重的,这些性状之间的协变模式也受到Gr损失的实质性影响。最明显的效果是gr突变系中与大胆有关的性状的关联。这项研究表明,在斑马鱼中,Gr不仅参与行为性状平均值的调节,而且还在于个体的行为特征如何相互关联并决定行为综合征。
    Glucocorticoids (GCs) have a wide spectrum of effects on animal behavior. A recently suggested effect involves determining the structure of individual differences, that is how the behavioral traits of an individual covary, forming the so-called behavioral syndromes. As GCs can exert their action in multiple ways, e.g., via rapid non-genomic effects or via the activation of two highly homologous members of the steroid receptor family acting as transcription factors, it is unclear how the GC modulation of behavioral syndromes takes place. We exploited a zebrafish line with a frameshift mutation in the gene encoding the GC receptor (Gr), to investigate this question. We found that lack of Gr altered the average score of several behavioral traits in the mutant line, determining reduced boldness, and increased activity and sociability. Critically, the pattern of covariation between these traits was also substantially affected by the loss of Gr. The most evident effect was an association of traits involved in boldness in the gr mutant line. This study reveals that, in zebrafish, Gr is not only involved in the modulation of the average value of behavioral traits, but also in how the behavioral traits of an individual are interrelated and determine the behavioral syndromes.
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  • 文章类型: Journal Article
    焦虑和癫痫在世界范围内很常见,是全球主要的健康问题。Fisetin,从五味子紫荆中分离出的一种类黄酮,具有广泛的生物活性可能是对抗与中枢神经系统(CNS)相关的疾病的有希望的替代方法。本研究旨在研究非塞素对成年斑马鱼的抗焦虑和抗惊厥作用。此外,进行分子对接模拟以改善结果。Fisetin不存在毒性,并在动物中引起抗焦虑行为和癫痫发作延迟。这种作用可以通过5-HT3A和/或5-HT3B受体的5-羟色胺神经传递发生。分子对接模拟表明,非瑟酮与5-HT3A受体的正构位点相互作用,与Trp156残基具有强烈的H键相互作用,邻苯二酚环的强大贡献,与拮抗剂共结晶抑制剂格拉司琼(CWB)的行为相似。Fisetin可能是对抗与中枢神经系统有关的疾病的有希望的替代品。关键词焦虑·五朵紫荆·丹尼奥·雷里奥·癫痫·非瑟丁。
    Anxiety and epilepsy are common worldwide and represent a primary global health concern. Fisetin, a flavonoid isolated from Bauhinia pentandra, has a wide range of biological activities may be a promising alternative to combat diseases related to the central nervous system (CNS). The present study aimed to investigate the anxiolytic and anticonvulsant effects of fisetin on adult zebrafish. Furthermore, molecular docking simulations were performed to improve the results. Fisetin did not present toxicity and caused anxiolytic behavior and delayed seizures in animals. This effect may occur through serotonin neurotransmission at 5-HT3A and/or 5-HT3B receptors. Molecular docking simulations showed that fisetin interacts with the orthosteric site of the 5-HT3A receptor with strong H-bond interactions with the Trp156 residue, with a strong contribution from the catechol ring, a behavior similar to that of the antagonist co-crystallized inhibitor granisetron (CWB). Fisetin may be a promising alternative to combat diseases related to the central nervous system. Keywords anxiety • Bauhinia pentandra • Danio rerio • epilepsy • fisetin.
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  • 文章类型: Journal Article
    染料工业在工业发展中起着至关重要的作用,为经济增长和进步做出重大贡献。然而,它的快速扩张导致了重大的环境问题,特别是由于未经处理或处理不当的染料废水的排放造成的水污染和生态系统退化。废水引入各种有害化学物质改变水质,耗氧水平,伤害水生生物,破坏食物链。染料污染也可以在环境中持续长时间,导致长期的生态破坏和威胁生物多样性。因此,研究了染料污染物对水生生态系统的复杂影响。最近,斑马鱼(Daniorerio)已被证明是这项研究的有效生物医学模型,因为其透明的胚胎允许实时观察发育过程和遗传接近度(约87%)用于人类研究多样化的生物反应。这篇综述强调了工业染料的各种毒理学作用,包括心血管毒性,神经毒性,遗传毒性,肝毒性,和发育毒性。在斑马鱼的不同发育阶段和染料浓度下观察到了这些影响。审查强调了该结构,染料的稳定性和化学成分显著影响毒理学影响,强调需要对染料降解进行详细调查,以更好地了解和减轻染料污染物带来的环境和健康风险。
    Dye industry plays an essential role in industrial development, contributing significantly to economic growth and progress. However, its rapid expansion has led to significant environmental concerns, especially water pollution and ecosystem degradation due to the discharge of untreated or inadequately treated dye effluents. The effluents introduce various harmful chemicals altering water quality, depleting oxygen levels, harming aquatic organisms, and disrupting food chains. Dye contamination can also persist in the environment for extended periods, leading to long-term ecological damage and threatening biodiversity. Therefore, the complex effects of dye pollutants on aquatic ecosystems have been comprehensively studied. Recently, zebrafish (Danio rerio) has proved to be an effective biomedical model for this study due to its transparent embryos allowing real-time observation of developmental processes and genetic proximity (approx. 87%) to humans for studying diverse biological responses. This review highlights the various toxicological effects of industrial dyes, including cardiovascular toxicity, neurotoxicity, genotoxicity, hepatotoxicity, and developmental toxicity. These effects have been observed at different developmental stages and dye concentrations in zebrafish. The review underscores that the structure, stability and chemical composition of dyes significantly influence toxicological impact, emphasizing the need for detailed investigation into dye degradation to better understand and mitigate the environmental and health risks posed by dye pollutants.
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  • 文章类型: Journal Article
    糖尿病在世界范围内普遍存在,>90%的病例被确定为2型糖尿病。高血糖(高血糖)是糖尿病的标志性症状,长期和不受控制的水平导致随后的并发症。动物模型已被用于研究这些并发症,其中包括视网膜病变,肾病,和周围神经病变。最近的研究集中在认知行为上,因为据报道在老年2型糖尿病患者中发生痴呆/认知缺陷的风险增加。在这次审查中,我们整理了从特定动物模型报告的数据(即,鼠标,rat,斑马鱼)已经检查了视网膜/视力(视网膜病)和大脑/认知的变化,包括db/db鼠标,Goto-Kakizaki老鼠,Zucker糖尿病肥胖大鼠,高脂肪饮食的啮齿动物和斑马鱼,和葡萄糖浸泡诱导的高血糖斑马鱼。之所以选择这些模型,是因为啮齿动物被广泛认为是研究糖尿病并发症的既定模型,而斑马鱼代表了这一领域的新模型。我们的目标是(1)总结与这些模型相关的已发表发现,(2)确定在两个组织中发生的疾病进展的细胞机制的相似性,和(3)解决了高血糖引起的视网膜变化先于或预测大脑并发症的假设。
    Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.
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  • 文章类型: Journal Article
    氨基甲酸酯类农药的广泛使用引起了众多的环境和健康问题,包括水污染和生物之间内分泌稳态的干扰。然而,关于灭多威对肠道微生物组成和生理功能的具体影响的研究仍然很少。本研究旨在调查环境相关浓度(0、0.05、0.10和0.20mg/L)的亚慢性灭多威暴露56天后斑马鱼细菌群落变化与肠道功能之间的复杂关系。我们的发现揭示了在斑马鱼肠道中显著的灭多威诱导的形态学变化,以绒毛缩短和断裂为特征。值得注意的是,灭多威暴露下调营养和能量代谢,和药物代谢在0.05-0.10mg/L,在上调皮质醇的同时,炎症相关基因,和凋亡标志物在0.20mg/L。这些表现表明生理应激强加和肠道微生物群平衡的破坏,影响代谢过程并激发低度炎症反应和凋亡级联反应。重要的是,肠道功能的变化与特定细菌分类群丰度的变化显着相关,包括Shewanella,鲁布杆菌,不动杆菌,芽孢杆菌,Luteolibacter,诺卡氏菌,去氟单胞菌,和拟杆菌属。总之,我们的研究强调了环境接触灭多威对水生生物的潜在不利影响,强调需要进一步研究以减轻其对环境健康和生态系统稳定性的影响。
    The widespread use of carbamate pesticides has led to numerous environmental and health concerns, including water contamination and perturbation of endocrine homeostasis among organisms. However, there remains a paucity of research elucidating the specific effects of methomyl on gut microbial composition and physiological functions. This study aimed to investigate the intricate relationship between changes in zebrafish bacterial communities and intestinal function after 56 days of sub-chronic methomyl exposure at environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings reveal significant methomyl-induced morphological changes in zebrafish intestines, characterized by villi shortening and breakage. Notably, methomyl exposure down-regulated nutrient and energy metabolism, and drug metabolism at 0.05-0.10 mg/L, while up-regulating cortisol, inflammation-related genes, and apoptotic markers at 0.20 mg/L. These manifestations indicate physiological stress imposition and disruption of gut microbiota equilibrium, impacting metabolic processes and instigating low-grade inflammatory responses and apoptotic cascades. Importantly, changes in intestinal function significantly correlated with shifts in specific bacterial taxa abundance, including Shewanella, Rubrobacter, Acinetobacter, Bacillus, Luteolibacter, Nocardia, Defluviimonas, and Bacteroides genus. In summary, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms, emphasizing the necessity for further research to mitigate its repercussions on environmental health and ecosystem stability.
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  • 文章类型: Journal Article
    鱼类性腺组织的冷冻保存是保持遗传变异的重要技术。然而,这项技术涉及使用低温管,具有低降解性的塑料容器,价格昂贵且在世界某些地区难以获得。因此,这项研究旨在评估明胶和羟丙甲纤维素硬胶囊作为一种可持续且易于获得的替代容器的功效,以替代冷冻管玻璃化斑马鱼(Daniorerio)性腺组织。将性腺组织(睾丸或卵巢)在冷冻管中玻璃化,硬明胶,和硬羟丙甲纤维素胶囊。明胶胶囊在保存精原细胞活力方面表现出与冷冻管相当的功效(33.03±10.03%和37.96±8.35%,分别),而羟丙甲纤维素胶囊的活力下降(18.38±2.09%)。未成熟的卵母细胞活力不受胶囊材料的影响,在所有卵母细胞阶段与冷冻管相比没有差异(初级生长:p<0.0001;皮质肺泡:p<0.0001;卵黄形成:p<0.0001)。线粒体活性和脂质过氧化在两种性腺组织的冷冻管和胶囊之间没有差异。然而,明胶胶囊(睾丸:147.2±32.32μg;卵巢:87.98±10.91μg)的抗氧化活性明显高于冷冻管(睾丸:81.04±26.05μg;卵巢:54.35±11.23μg)和羟丙甲纤维素胶囊(睾丸:62.36±17.10μg;卵巢:63.96±7.51μg),可能是由于明胶固有的抗氧化特性。在这项研究中获得的结果表明,冷冻管可以被明胶胶囊替代,用于玻璃化斑马鱼的两个性腺组织,是一种可持续和可获得的替代品,因为它是一种低成本和环保的容器。
    Cryopreservation of fish gonadal tissue is an important technique for preserving genetic variability. However, this technique involves the use of cryotubes, plastic containers with low degradability that are expensive and difficult to obtain in certain parts of the world. Therefore, this study aimed to evaluate the efficiency of gelatin and hypromellose hard capsules as a sustainable and accessible alternative container to the cryotube for vitrification of zebrafish (Danio rerio) gonadal tissue. The gonadal tissues (testicular or ovarian) were vitrified in cryotubes, hard-gelatin, and hard-hypromellose capsules. Gelatin capsules exhibited comparable efficacy to cryotubes in preserving spermatogonia viability (33.03 ± 10.03 % and 37.96 ± 8.35 %, respectively), whereas hypromellose capsules showed decreased viability (18.38 ± 2.09 %). Immature oocyte viability remained unaffected by the capsule materials, with no difference compared to cryotubes at all oocyte stages (Primary Growth: p < 0.0001; Cortical Alveolar: p < 0.0001; Vitellogenic: p < 0.0001). Mitochondrial activity and lipid peroxidation demonstrated no difference among cryotubes and capsules for both gonadal tissues. However, antioxidant activity was notably higher in gelatin capsules (Testes: 147.2 ± 32.32 μg; Ovary: 87.98 ± 10.91 μg) than in cryotubes (Testes: 81.04 ± 26.05 μg; Ovary: 54.35 ± 11.23 μg) and hypromellose capsules (Testes: 62.36 ± 17.10 μg; Ovary: 63.96 ± 7.51 μg), likely due to the inherent antioxidant properties of gelatin. The results obtained in this study demonstrate that the cryotube can be replaced by gelatin capsules for vitrification of both gonadal tissues of zebrafish, being a sustainable and accessible alternative as it is a low-cost and environmentally friendly container.
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  • 文章类型: Journal Article
    传统上在亚马逊地区用于药用的植物性物种紫荆花(Leguminosae-Cercidoideae)。
    在斑马鱼(Daniorerio)中评估了来自B.guianensis叶和茎(HELBg和HESBg)的乙醇提取物的急性毒性,重点是胚胎发育阶段和成人改变。
    在LC-DAD-MS/MS上分析提取物。斑马鱼卵分别接种HELBg和HESBg浓度(0.25、0.5、0.75、1.0和1.5µg/mL),观察96小时。用单次口服剂量(100、200、500、1000和2000mg/kg)的HELBg和HESBg治疗成年斑马鱼,观察48小时。
    HELBg和HESBg分析检测到55种化合物。两种提取物都表现出毒性,包括在较高剂量HERBg下的胚胎凝固和在所有剂量HESBg下的胚胎中没有心跳。观察到行为变化;在最高剂量下发现成年斑马鱼的组织改变,主要在肝脏,肠,和肾脏,因为HELBg和HESBg的影响。HESBg的LD50为1717mg/kg,而HELBg超过2000mg/kg的限制剂量。
    广西双歧杆菌提取物的急性毒性研究显示出显著的毒性潜力,强调对胚胎和成年斑马鱼的影响。结果表明该物种制剂的相对安全性,鼓励关于潜在生物活性的进一步临床试验。
    UNASSIGNED: The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes.
    UNASSIGNED: The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations.
    UNASSIGNED: Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h.
    UNASSIGNED: HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg.
    UNASSIGNED: The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.
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  • 文章类型: Journal Article
    本研究旨在确定碳纳米管(CNTs)的潜在毒理学效应,用乙二胺(ED)和硼酸(BA)对水生生物进行修饰。具体来说,研究集中在形态学上,生理,斑马鱼(Daniorerio)胚胎和幼虫的组织病理学免疫组织化学反应,通过应用不同浓度的碳纳米管,CNT-ED,和CNT-ED-BA(控制,5、10和20mg/L)。结果表明,20mg/L碳纳米管纳米颗粒对斑马鱼幼虫具有毒性,死亡率随着CNT和CNT-ED浓度的增加而增加,在最高CNT浓度下达到36.7%。最高剂量导致相当大的变性,坏死,DNA损伤,和细胞凋亡,组织病理学和免疫组织化学测试证明。相比之下,尽管浓度很高,CNT-ED-BA纳米颗粒表现出低毒性。行为研究表明,与CNT-ED-BA纳米颗粒相比,CNT和CNT-ED纳米颗粒对感觉运动功能的影响更大。这些发现表明,用硼酸修饰纳米表面,产生硼酰胺酸,可以降低由CNT和CNT-ED引起的毒性。
    This study aimed to determine the potential toxicological effects of carbon nanotubes (CNTs), their modifications with ethylenediamine (ED) and boric acid (BA) on aquatic organisms. Specifically, the research focused on the morphological, physiological, and histopathological-immuno-histochemical responses in zebrafish (Danio rerio) embryos and larvae, via applying different concentrations of CNTs, CNT-ED, and CNT-ED-BA (Control, 5, 10, and 20 mg/L). The results indicated that 20 mg/L CNT nanoparticles were toxic to zebrafish larvae, with mortality rates increasing with CNT and CNT-ED concentrations, reaching 36.7 % at the highest CNT concentration. The highest dose caused considerable degeneration, necrosis, DNA damage, and apoptosis, as evidenced by histopathological and immunohistochemical tests. In contrast, despite their high concentration, CNT-ED-BA nanoparticles exhibited low toxicity. Behavioral studies revealed that CNT and CNT-ED nanoparticles had a more significant impact on sensory-motor functions compared to CNT-ED-BA nanoparticles. These findings suggest that modifying the nanosurface with boric acid, resulting in boramidic acid, can reduce the toxicity induced by CNT and CNT-ED.
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  • 文章类型: Journal Article
    龋齿是世界范围内人类常见的口腔疾病,由产酸细菌变形链球菌引起的。预防龋齿的合成药物和抗生素的使用一直在增加,但这会导致严重的副作用.为了解决这个问题,发展中国家和发达国家已将草药作为合成药物的替代品,用于治疗和预防龋齿。因此,迫切需要植物衍生产品来治疗这些疾病。BacopaMonnieri,一种有据可查的药用植物,含有52种植物化合物,包括称为积雪草酸(ASTA)的五环三萜类代谢物。因此,这项研究旨在证明,第一次,植物化合物ASTA对变形链球菌的抗菌活性。研究结果表明,ASTA显著抑制变异链球菌的生长和酸性等毒力因子的产生,酸化,和eDNA合成。分子对接分析评估了ASTA对变异链球菌毒力基因的潜在活性,包括VicR和GtfC.此外,对人口腔上皮细胞进行ASTA的毒性评估,未观察到形态学变化。使用Daniorerio(斑马鱼)的体内分析证实,ASTA处理通过阻碍变形链球菌的肠道定植,显着提高了感染鱼的存活率。此外,ASTA对变异链球菌感染的病理症状的疾病保护潜力已通过g的组织病理学检查得到证实,gut,gut还有肾.总的来说,这些研究结果表明,ASTA可能是治疗和预防变形链球菌口腔感染的一种有前景的治疗和替代药物.
    Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTA may be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans.
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  • 文章类型: Journal Article
    长时间的高血糖会导致长期的视力并发症和认知障碍的风险增加。高血糖还赋予细胞渗透负荷/压力。我们评估了持续4周或8周高血糖后斑马鱼大脑和视网膜的行为和神经化学变化。在每个时间点,行为评估使用三室选择任务和视电机反应;然后收集组织和炎症标记物的水平,紧密连接蛋白,和使用西方印迹确定的神经递质。4周后,v-rel网状内皮增生病病毒癌基因同源物A(禽)(RelA;NF-kB亚基)的脑水平,IkB激酶(IKK),和胶质纤维酸性蛋白(GFAP)显着升高;小带闭塞-1(ZO-1)的差异,claudin-5,谷氨酸脱羧酶(GAD),酪氨酸羟化酶(TH)无显著差异。在视网膜中,仅在TH(下降)中观察到显着差异,RelA(增加),和GFAP(增加)水平。还观察到初始选择潜伏期和辨别比的葡萄糖特异性差异。8周后,Rela,GAD,和TH在两个组织中都显着升高;IKK和GFAP水平也升高,虽然不是很重要。ZO-1和claudin-5水平在视网膜中渗透降低,但在葡萄糖处理的大脑中显示出增加的趋势。区分率的差异是由渗透负荷驱动的。在两个年龄段,经过葡萄糖处理的鱼的OMR均增加。视网膜血管系统的体内分析提示4周后血管较厚,但在8周时血管更薄。体外,葡萄糖治疗减少了3B-11内皮细胞中节点和网状物的形成,表明形成血管网的能力降低。总的来说,高血糖引发强烈的炎症反应,导致紧密连接和神经元标志物的初始趋势变化.暴露4周后,在葡萄糖处理的鱼中观察到大多数差异,表明对葡萄糖代谢的影响与渗透负荷无关。8周后,炎症反应仍然存在,并观察到葡萄糖对神经递质标志物的特异性影响.渗透差异影响认知行为和视网膜蛋白质水平;大脑中的蛋白质水平显示出葡萄糖驱动的变化。因此,我们不仅观察到视网膜和大脑对葡萄糖损伤的不同敏感性,但也有不同的细胞反应,提示高血糖在细胞水平引起复杂的影响和/或斑马鱼能够补偿持续的高血糖水平。
    Prolonged hyperglycemia causes long-term vision complications and an increased risk of cognitive deficits. High blood sugar also confers an osmotic load/stress to cells. We assessed behavioral and neurochemical changes in zebrafish brain and retina following prolonged hyperglycemia for 4-weeks or 8-weeks. At each time point, behavior was assessed using 3-chamber choice task and optomotor response; tissue was then collected and levels of inflammatory markers, tight junction proteins, and neurotransmitters determined using Western Blots. After 4-weeks, brain levels of v-rel reticuloendotheliosis viral oncogene homolog A (avian) (RelA; NF-kB subunit), IkB kinase (IKK), and glial fibrillary acidic protein (GFAP) were significantly elevated; differences in zonula occludens-1 (ZO-1), claudin-5, glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were not significant. In retina, significant differences were observed only for TH (decreased), Rel A (increased), and GFAP (increased) levels. Glucose-specific differences in initial choice latency and discrimination ratios were also observed. After 8-weeks, RelA, GAD, and TH were significantly elevated in both tissues; IKK and GFAP levels were also elevated, though not significantly. ZO-1 and claudin-5 levels osmotically decreased in retina but displayed an increasing trend in glucose-treated brains. Differences in discrimination ratio were driven by osmotic load. OMRs increased in glucose-treated fish at both ages. In vivo analysis of retinal vasculature suggested thicker vessels after 4-weeks, but thinner vessels at 8-weeks. In vitro, glucose treatment reduced formation of nodes and meshes in 3B-11 endothelial cells, suggesting a reduced ability to form a vascular network. Overall, hyperglycemia triggered a strong inflammatory response causing initial trending changes in tight junction and neuronal markers. Most differences after 4-weeks of exposure were observed in glucose-treated fish suggesting effects on glucose metabolism independent of osmotic load. After 8-weeks, the inflammatory response remained and glucose-specific effects on neurotransmitter markers were observed. Osmotic differences impacted cognitive behavior and retinal protein levels; protein levels in brain displayed glucose-driven changes. Thus, we not only observed differential sensitivities of retina and brain to glucose-insult, but also different cellular responses, suggesting hyperglycemia causes complex effects at the cellular level and/or that zebrafish are able to compensate for the continued high blood glucose levels.
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