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Role of Actinobacteria and Coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression

机译:猕猴桃和奇杆菌在氯胺酮抗抑郁作用中的作用在抑郁症炎症模型中的作用

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摘要

Ketamine, an N-methyl-D-aspartic acid receptor (NMDAR) antagonist, elicits rapid-acting and sustained antidepressant effects in treatment-resistant depressed patients. Accumulating evidence suggests that gut microbiota via the gut-brain axis play a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. Here we investigated the role of gut microbiota in the antidepressant effects of ketamine in lipopolysaccharide (LPS)-induced inflammation model of depression. Ketamine (10 mg/kg) significantly attenuated the increased immobility time in forced swimming test (FST), which was associated with the improvements in alpha-diversity, consisting of Shannon, Simpson and Chao 1 indices. In addition to alpha-diversity, beta-diversity, such as principal coordinates analysis (PCoA), and linear discriminant analysis (LDA) coupled with effect size measurements (LEfSe), showed a differential profile after ketamine treatment. Furthermore, a total of 30 bacteria were significantly altered in the LPS + saline treated mice and LPS + ketamine treated mice. Interestingly, two bacteria, including the phylum Actinobacteria and the class Coriobacteriia were significantly correlated with the immobility time of FST. Importantly, the receiver operating characteristic (ROC) curves demonstrated that the phylum Actinobacteria and the class Coriobacteriia were potential biomarker for the antidepressant effects of ketamine in an inflammation model. These findings suggest that antidepressant effects of ketamine might be related to the regulation of abnormal composition of gut microbiota, and that the phylum Actinobacteria and the class Coriobacteriia might be potential biomarkers for ketamine's antidepressant efficacy.
机译:氯胺酮,N-甲基-D-天冬氨酸受体(NMDAR)拮抗剂,引发在治疗抗抑郁症患者中的快速作用和持续的抗抑郁作用。积累证据表明,通过肠脑轴的肠道微生物会在抑郁症发病机制中发挥作用,从而有助于某些化合物的抗抑郁作用。在这里,我们调查了肠道微生物群在氯胺酮(LPS)诱导的抑郁症炎症模型中的氯胺酮抗抑郁作用中的作用。氯胺酮(10 mg / kg)显着减弱了强制游泳试验(FST)的不动时间增加,这与alpha-多样性的改进有关,由Shannon,Simpson和Chao 1索引组成。除了α-多样性,如主坐标分析(PCOA)和与效果尺寸测量(LEFSE)相结合的主要坐标分析(PCOA)和线性判别分析(LDA),在氯胺酮治疗后显示出差异型材。此外,在LPS +盐水处理的小鼠和LPS +氯胺酮处理小鼠中,总共30种细菌显着改变。有趣的是,两种细菌,包括肌动菌和阶级的肌杆菌和血管杆菌与FST的不可动行显着相关。重要的是,接收器操作特征(ROC)曲线证明了肌动菌和类角曲杆菌是潜在的氯胺酮在炎症模型中的抗抑郁作用的潜在生物标志物。这些发现表明氯胺酮的抗抑郁作用可能与肠道微生物异常组成的调节有关,并且体肌肌科和阶级的角质杆菌可能是用于氯胺酮的抗抑郁效果的潜在生物标志物。

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  • 作者单位

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Soochow Univ Dept Internal Med Affiliated Hosp 3 Changzhou 213003 Peoples R China;

    Soochow Univ Dept Internal Med Affiliated Hosp 3 Changzhou 213003 Peoples R China;

    Soochow Univ Dept Internal Med Affiliated Hosp 3 Changzhou 213003 Peoples R China;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Chiba Univ Div Clin Neurosci Ctr Forens Mental Hlth Chiba 2608670 Japan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

    Huazhong Univ Sci &

    Technol Tongii Med Coll Tone Hosp Dept Anesthesiol 1095 Jiefang Ave Wuhan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    Ketamine; Depression; Lipopolysaccharide; Gut microbiota;

    机译:氯胺酮;抑郁症;脂多糖;肠道微生物;

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