MiR-29a-3p ameliorate behavioral deficiency in hypoxia-ischemia brain damage in neonatal mice by inhibiting BTG2.

It has been reported that miR-29a-3p played a part in series neurological disorders. However, it remains unclear whether miR-29a-3p participate in the pathological mechanism in hypoxia-ischemia (HI) brain injury. In this study, we detected the change of miR-29a-3p level in the ipsilateral cortex following HI brain injury and found that miR-29a-3p was significantly increased at 3 days in the ipsilateral cortex following HI insult in neonatal mice. Therefore, we further explored the role of miR-29a-3p in HI brain injury and its molecular mechanism. The results showed that miR-29a-3p mimics attenuated and miR-29a-3p antagomir aggravated brain infarction volume at 3 days following HI insult. We further found that overexpression of miR-29a-3p also suppressed apoptosis and neuroinflammation, reduced synaptic loss and prevent HI-induced microglial morphological changes 3 days following HI insult. Neurobehavioral tests revealed that overexpression of miR-29a-3p could improve both short-term and long-term behavioral defects after HI injury. Furthermore, we proved that miR-29a-3p targets B-cell translocation gene 2 (BTG2) and further inhibits the expression of Bax by luciferase reporter assay and qRT-PCR. Moreover, overexpression of miR-29a-3p, by applying liposomes through intranasal route, could also achieve the same therapeutic effect in HI injury. Our data showed that by inhibiting BTG2/Bax, increasing level of miR-29a-3p might serve as a strategy to prevent brain damage and behavioral deficiency in HI.