Background: SAHA was reported to enhance the expression of miR-129-5p, which was predicted to bind to 3' UTR of CASP-6, a gene playing crucial roles in the pathogenesis of memory impairment. Whether SAHA/miR-129-5p/CASP-6 is involved in the pathogenesis of prenatal exposure to sevoflurane remains to be explored.
Methods: Morris water maze test was performed to evaluate the functional parameters of learning and memory. Quantitative real-time qPCR was carried out to analyze the expression of miRNAs and CASP-6 mRNA under different conditions.
Results: Sevoflurane exposure of pregnant rats and SAHA treatment of the offspring had no effect on the blood gases, litter size, survival rate and weight. SAHA administration remarkably reversed the learning and memory impairment in prenatal rats caused by sevoflurane exposure. Mechanistically, the abnormal expression of miR-129-5p and CASP-6 in the offspring of pregnant rats exposed to sevoflurane was effectively restored by SAHA treatment. The luciferase activity of CASP-6 vector was effectively inhibited by miR-129-5p in primary neuron cells of rats. Moreover, the expression of CASP-6 mRNA and protein was significantly suppressed by miR-129-5p and SAHA treatment in a dose-dependent manner.
Conclusion: Our work demonstrated that the administration of SAHA suppressed the expression of CASP-6 via modulating the expression of miR-129-5p, and SAHA may rescue the apoptosis of neurons caused by exposure to sevoflurane. The underlying mechanism might be the ability of SAHA to relieve learning and memory impairment in the offspring of the pregnant rats exposed to sevoflurane.
Keywords: CASP-6; Learning and memory; SAHA; Sevoflurane; miR-129-5p; miRNA.
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