MicroRNA-34a regulates brain-derived neurotrophic factor in an intracerebral hemorrhage model

: Intracerebral hemorrhages (ICHs) are devastating neurological events frequently resulting in a serious negative prognosis. The exact physiological and disease processes involved in ICHs are complex, but are thought to involve microRNAs (miRNAs), 22 nucleotide small noncoding RNAs that control a variety of normal physiological and disease processes. In this study, we show that a miRNA, miR-34a, regulates BDNF in a model of ICH injury. In particular, we assessed the impact of AM34a, an inhibitor of miR-34a, on the toxicity of thrombin-induced apoptosis and on BDNF-mediated signaling. We investigated the increased expression of miR-34a after an ICH-induced thrombin toxicity injury using a real-time polymerase chain reaction (RT-PCR) and evaluated miR-34a as a therapeutic target. Apoptosis was confirmed by 4 ,6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenindUTP-biotin nick-end labeling (TUNEL). The number of apoptotic cells detected by TUNEL after ICH injury was decreased by AM34a. Additionally, the ICH injury model treated with AM34a had a significantly lower caspase-3 level. We performed western blot analyses for BDNF, phosphorylated Akt, and phosphorylated ERK. The levels of BDNF were significantly higher in samples treated with AM34a. Furthermore, the level of phosphorylated Akt and phosphorylated ERK were significantly higher under AM34a. In conclusion, we demonstrated a distinct miRNA expression pattern after an in vitro ICH injury model, and modulation of this pattern can have therapeutic potential. miR-34a antagomir reduced cell death and enhanced neurological recovery by activating the BDNF pro-survival pathway. This suggests that inhibiting miR-34a might be a potential therapeutic target in ICH.

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