microRNA‐124 attenuates isoflurane‐induced neurological deficits in neonatal rats via binding to EGR1

Isoflurane anesthesia induces neuroapoptosis in the development of the brain. In this study, neonatal rats and hippocampal neurons were subjected to isoflurane exposure, in which the effect of miR‐124 on the neurological deficits induced by isoflurane was evaluated. Isoflurane anesthesia models were induced in neonatal SD rats aged 7 days and then treated with miR‐124 agomir, miR‐124 antagomir, or LV‐CMV‐early growth response 1 (EGR1) plasmids. Then, the spatial learning and memory ability of rats were evaluated by Morris water maze. Furthermore, primary hippocampal neurons cultured 7 days were also exposed to isoflurane and transfected with miR‐124 agomir, miR‐124 antagomir, or LV‐CMV‐EGR1 plasmids. The targeting relationship of miR‐124 and EGR1 was verified by the dual‐luciferase reporter gene assay. To identify the effect of miR‐124 on neuron activities, the viability and apoptosis of hippocampal neurons were assessed. In response to isoflurane exposure, miR‐124 expression was reduced and EGR1 expression was increased in the hippocampal tissues and neurons. The isoflurane anesthesia damaged rats' spatial learning and memory ability, and reduced viability, and promoted apoptosis of hippocampal neurons. EGR1 was targeted and negatively regulated by miR‐124. The treatment of miR‐124 agomir improved rats' spatial learning and memory ability and notably increased hippocampal neuron viability and resistance to apoptosis, corresponding to an increased brain‐derived neurotrophic factor (BDNF) expression, inhibited expression of proapoptotic factors (cleaved‐Caspase‐3 and Bax), and enhanced the expression of antiapoptotic factor (Bcl‐2). Upregulated miR‐124 inhibited the expression of EGR1, by which mechanism miR‐124 reduced the neurological deficits induced by isoflurane in neonatal rats through inhibiting apoptosis of hippocampal neurons.

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