Expression levels of microRNA-199 and hypoxia-inducible factor-1 alpha in brain tissue of patients with intractable epilepsy

Int J Neurosci. 2016;126(4):326-34. doi: 10.3109/00207454.2014.994209. Epub 2015 Sep 30.

Abstract

Objectives: During the last decade, experimental evidence has demonstrated an important role of hypoxia, which leads to neuronal cell death and angiogenesis, in the mechanisms of seizure precipitation and recurrence. MicroRNA-199 targets hypoxia-inducible factor-1alpha (HIF-1α), which has recently been implicated in the pathophysiology of the hypoxic state and brain injury. However, little is known about the roles of MicroRNA-199 and HIF-1α in the human epileptogenic process.

Design and methods: In this study, we investigated the expression of miR-199a-5p, miR-199b-5p and HIF-1α using real-time PCR, immunohistochemistry and western blots in the temporal neocortex of twenty four patients with intractable epilepsy and twelve control subjects.

Results: Compared with the control group, the expression of miR-199a-5p and miR-199b-5p was significantly lower in epileptic brain tissues (p < 0.05). The levels of HIF-1α mRNA and protein were highly up-regulated in epileptic brain tissues compared with those of control subjects (p < 0.05).

Conclusion: These data suggest that the abnormal expression of miR-199 and HIF-1α in epileptic brain tissue may be involved in the pathophysiology of human epilepsy and that the expression of HIF-1α may be regulated by miR-199. These findings may provide new insights into the treatment of epilepsy.

Keywords: epilepsy; hypoxia; hypoxia-inducible factor-1α; miRNA-199; recurrent seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Drug Resistant Epilepsy / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Temporal Lobe / metabolism*
  • Young Adult

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • mirn199 microRNA, human