Downregulation of microRNA-448 improves isoflurane-induced learning and memory impairment in rats

Mol Med Rep. 2017 Aug;16(2):1578-1583. doi: 10.3892/mmr.2017.6724. Epub 2017 Jun 8.

Abstract

The present study aimed to investigate the potential role of microRNA‑448 (miR‑448) in isoflurane-induced learning and memory impairment in rats. Sprague‑Dawley rats were used for the construction of isoflurane‑treated models. The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding the following para-meters: Swimming speed, escape latency and time in original quadrant. Influences of isoflurane on neuron apoptosis and miR‑448 expression in rat hippocampus tissue were analyzed by flow cytometry and reverse transcription‑quantitative polymerase chain reaction, respectively. Furthermore, the effects of miR‑448 on the expression of cell apoptosis‑associated proteins were investigated by flow cytometry. The results demonstrated that isoflurane treatment induced higher escape latency and lower time spent in original quadrant compared with the control rats. In addition, isoflurane treatment induced neuron apoptosis and miR‑448 was highly expressed in the hippocampal tissue of isoflurane‑treated rats. Furthermore, Bcl‑x was significantly downregulated while caspase‑3 expression was upregulated by an miR‑448 inhibitor. Combined the results of the current study indicate that miR‑448 knockdown may have pivotal roles in improving isoflurane-induced learning and memory impairment via suppressing neuron apoptosis.

MeSH terms

  • Animals
  • Antagomirs / metabolism
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Down-Regulation
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Isoflurane / pharmacology*
  • Male
  • Maze Learning / drug effects*
  • Memory / drug effects*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antagomirs
  • MicroRNAs
  • bcl-2-Associated X Protein
  • Isoflurane
  • Caspase 3