MicroRNA-9 Mediated the Protective Effect of Ferulic Acid on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Abstract

Abbreviations: HIBD, hypoxic-ischemic brain damage; HI, hypoxia-ischemia; FA, ferulic acid; SF, sodium ferulic; qRT-PCR, quantitative real-time PCR; AchE, acetylcholinesterase; PSD-95, postsynaptic density protein-95; miR-9, microRNA-9; LNA-miR-9: locked nucleic acid-miR-9; DG, dentate gyrus.Abstract--Neonatal hypoxic-ischemic brain damage (NHIBD) leads to cognitive and memory impairments, and there is no effective clinical treatment. Ferulic acid (FA)is found within members of the genus Angelica, reportedly shows protective effects on neuronal damage; however, the mechanism of the protective effects of FA on rats following NHIBD remains unclear. Using the Morris water maze task, we herein found that the impairment of spatial memory formation in adult rats exposed to NHIBD was significantly reversed by FA treatment and the administration of LNA-miR-9. RT-PCR analyses revealed that miRNA-9 was significantly increased in the hippocampus of neonatal rats and neuronal PC12 cells following NHIBD and that FA and LNA-miR-9 both inhibited the expression of miRNA-9, suggesting that the therapeutic effect of FA was mainly attributed to the inhibition of miRNA-9 expression. Indeed, the silencing of miR-9 by LNA-miR-9 or FA similarly attenuated neuronal damage and cerebral atrophy in the rat hippocampus after NHIBD, which was consistent with the restored expression levels of brain-derived neurotrophic factor (BDNF). Therefore, FA treatment may protect against neuronal death through the inhibition of miRNA-9 induction in the rat hippocampus following hypoxic-ischemic damage.