Up-regulation of microRNA-223 inhibits brain injury and hippocampal neuron apoptosis of rats after febrile seizure through the NLRP3-Caspase-1 signaling pathway

Biomed Pharmacother. 2019 Jun:114:108683. doi: 10.1016/j.biopha.2019.108683. Epub 2019 Apr 1.

Abstract

Objective: This study is conducted to explore the role of microRNA-223 (miR-223) in brain injury and apoptosis of hippocampal neurons through the NLRP3-Caspase-1 signaling pathway in febrile seizure (FS) rats.

Methods: The models of FS were induced in rats by hot water-bath, which were stereotactically injected with miR-223 mimics and mimics negative control (NC) to perturb the expression of miR-223. A series of experiments was conducted to find out the potential mechanisms of miR-223 on convulsion attack, learning and memory ability, pathological injury of hippocampal neurons, inflammatory injury, apoptosis of hippocampal neurons in FS rats. Besides, the targeting relationship between miR-223 and NLRP3 was also verified.

Results: Low expression of miR-223 was found in hippocampus tissues of FS rats. Up-regulation of miR-223 alleviated convulsion attack and improved learning and memory ability, while inhibiting pathological injury of hippocampal neurons and inflammatory injury in FS rats. Up-regulation of miR-223 promoted the survival of hippocampal neurons and inhibited their apoptosis in FS rats. MiR-223 inhibited the activation of NLRP3-Caspase-1 signaling pathway in hippocampus tissues of FS rats by inhibiting NLRP3.

Conclusion: The inhibited expression of miR-223 after FS may participate in the activation of the NLRP3-Caspase-1 signaling pathway, resulting in brain injury and apoptosis of hippocampal neurons in rat models of FS.

Keywords: Brain injury; Febrile seizure; Hippocampal neurons; Inflammatory injury; Learning and memory ability; MicroRNA-223; NLRP3-Caspase-1 signaling pathway.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Brain Injuries / genetics*
  • Brain Injuries / pathology
  • Caspase 1 / genetics*
  • Hippocampus / pathology
  • Learning / physiology
  • Memory / physiology
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Neurons / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / genetics
  • Seizures / pathology
  • Seizures, Febrile / genetics*
  • Signal Transduction / genetics
  • Transcriptional Activation / genetics
  • Up-Regulation / genetics*

Substances

  • MIRN223 microRNA, rat
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Caspase 1