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

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.