• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Contribution of DNA methyltransferases to spared nerve injury induced depression partially through epigenetically repressing Bdnf in hippocampus: Reversal by ketamine
【24h】

Contribution of DNA methyltransferases to spared nerve injury induced depression partially through epigenetically repressing Bdnf in hippocampus: Reversal by ketamine

机译：DNA甲基转移酶的贡献部分通过在海马中的外延抑制BDNF部分地进行神经损伤诱导抑郁症：通过氯胺酮逆转

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Long-lasting pain can induce depression, which seriously affects life quality of the patients, but little is known about the underlying mechanism. Chronic neuropathic pain can modulate DNA methylation in target genes related to neuroplasticity and mood regulation, which was induced by DNA methyltransferases (DNMTs). Methylation changes of brain-derived neurotrophic factor (Bdnf) in the hippocampus are critical for neuropathic pain and depression. Thus, we hypothesized that DNMTs are required for depression genesis, probably by repressing hippocampus Bdnf gene expression in rats with neuropathic pain, which can be rescued by ketamine. In the present study, rats were randomly subjected to spared nerve injury (SNI) or sham surgery. SNI upregulated DNMTs and downregulated Bdnf and exon I in the hippocampus and induced depression behaviors, whereas blocking the upregulation of DNMTs with RG108 alleviated SNI-induced depression by up-regulation of the expression of Bdnf and exon I. In addition, we showed that a single dose of ketamine could ameliorate SNIinduced depression-like behaviors, which was related to normalization of DNMTs and Bdnf. In conclusion, our study suggested that DNMTs-induced decreased expression of Bdnf may induce the comorbid of pain and depression, which can be prevented by ketamine.
机译：长期疼痛可诱发抑郁，严重影响患者的生活质量，但对其潜在机制知之甚少。慢性神经病理性疼痛可调节DNA甲基转移酶（DNMT）诱导的神经可塑性和情绪调节相关靶基因的DNA甲基化。海马脑源性神经营养因子（Bdnf）的甲基化变化对神经病理性疼痛和抑郁至关重要。因此，我们假设DNMT是抑郁症发生所必需的，可能是通过抑制神经病理性疼痛大鼠的海马Bdnf基因表达，氯胺酮可以挽救这种疼痛。在本研究中，大鼠随机接受备用神经损伤（SNI）或假手术。SNI上调海马中的DNMT，下调Bdnf和外显子I，并诱导抑郁行为，而用RG108阻断DNMT的上调，通过上调Bdnf和外显子I的表达，减轻SNI诱导的抑郁。此外，我们发现单剂量氯胺酮可以改善SNI诱导的抑郁样行为，这与DNMT和Bdnf的正常化有关。总之，我们的研究表明，DNMTs诱导的Bdnf表达降低可能导致疼痛和抑郁的共病，氯胺酮可以预防这种共病。

著录项

  • 来源
  • 作者

    Liu Ru; Wu Xin-miao; He Xue; Wang Run-zhu; Yin Xiao-yu; Zhou Feng; Ji Mu-huo; Shen Jin-chun;

  • 作者单位

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Med Univ Affiliated Hosp 2 Dept Anesthesiol Nanjing Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Anesthesiol Nanjing Peoples R China;

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

    DNMTs; Bdnf; Neuropathic pain; Depression; Ketamine;

    机译：dnmts;bdnf;神经性疼痛;抑郁症;氯胺酮;

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号