Increasing evidence has demonstrated a vital role of microRNAs (miRNAs) in diverse biological processes. However, their functions in developing brain with hypoxia-ischemia (HI) remain largely unknown. Through a miRNA microarray analysis in a P10 rat model of cerebral HI, we found that miR-30d-5p was one of the most deregulated miRNAs in neonatal brains in response to HI. MiR-30d-5p was downregulated in a time-dependent manner in brain cortex after HI, which was accompanied by increased expression of Beclin1 both at transcript and protein levels. Increase of miR-30d-5p by agomir (AG) resulted in reduction of autophagy and increase of apoptosis, whereas inhibition of miR-30d-5p by antagomir (AT) enhanced autophagy and inhibited apoptosis in rat brains after HI. Moreover, miR-30d-5p AG increased infarct volume, delayed recovery of neurological function, and impaired improvement of spatial memory ability. MiR-30d-5p AT decreased infarct volume, promoted neurological recovery, and improved behavior performance of rats subjected to HI. Collectively, these results indicated that miR-30d-5p modulated survival programs of neural cell by regulating autophagy and apoptosis.
Keywords: Autophagy; Beclin1; Hypoxic–ischemic; MicroRNA; Neonatal.
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