Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats

Abstract

Exposure to sevoflurane in neonatal rats could induce learning deficits and abnormal social behaviors, but the specific molecular mechanism is unknown. Postnatal day-7 SD rats were treated with 3% sevoflurane plus 30% oxygen/air or 30% oxygen/air. As the rats grew, the Morris water maze (MWM) and fear conditioning tests were performed to evaluate cognitive function, while the expression of LIMK1 was analyzed by western blot. Luciferase reporter assay was performed to investigate the interaction between LIMK1 and miR-27b. The expression of miR-27b was measured by real-time polymerase chain reaction (PCR) after exposure to sevoflurane. Once the miR-27b inhibitor was transfected into the neurons, the expression of LIMK1 was analyzed by real-time PCR and western blot. Exposure to sevoflurane in neonatal rats induced memory and learning impairments according to the MWM and fear conditioning tests. Sevoflurane increased the expression of miR-27b and reduced the expression of LIMK1 in the brain tissues of rats compared to the control group. The results of the luciferase reporter assay showed that LIMK1 was a direct target of miR-27b. In the primary neurons, the inhibition of miR-27b could reverse the down-regulating effects of sevoflurane on LIMK1 expression. We suggest that sevoflurane-induced learning and memory impairments in rats might be mediated via the miR-27b-LIMK1-signaling pathway.

• Learning and memory impairments
• LIMK1
• miR-27b
• neonatal rats
• sevoflurane

Acknowledgements

This study was sponsored by the Program of Shanghai Subject Chief Scientist [grant number: 16XD1401800] and by research funds from the National Science Foundation of China [grant number: 81571028].

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. This study was sponsored by the Program of Shanghai Subject Chief Scientist [grant number: 16XD1401800] and by research funds from the National Science Foundation of China [grant number: 81571028].