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Published on: May 12, 2018
MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2
Lei Wang1, Mengliang Zheng1, Shuishui Wu1
1Department of Anesthesia, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
Abstract:
Sevoflurane is a commonly used inhalation anesthetic. Sevoflurane-induced neuroapoptosis and cognitive impairments in animals are widely reported, however, the underlying molecular mechanisms remain largely unknown. The results of the present study demonstrated that sevoflurane anesthesia induced spatial memory impairments in rats, as determined by the Morris water maze test. Mechanistically, the current study demonstrated that sevoflurane administration significantly enhanced the expression of microRNA (miR)‑188‑3p. Furthermore, inhibition of miR‑188‑3p using lentiviral miR‑188‑3p inhibitors attenuated sevoflurane‑induced cognitive impairments in rats. The present study also demonstrated that miR‑188‑3p targeted MDM2 proto‑oncogene (MDM2) and negatively regulated the expression of MDM2, as determined by luciferase assays, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Furthermore, decreased abundance of MDM2 following transfection with miR‑188‑3p mimics was associated with increased stability of p53 protein. Suppression of p53 activity using the specific p53 inhibitor pifithrin‑α alleviated sevoflurane‑induced neuroapoptosis. These results indicate that the miR‑188‑3p‑MDM2‑p53 axis may have a critical role in sevoflurane‑induced cognitive dysfunction. Therefore, miR‑188‑3p may be a potential target for the treatment of sevoflurane‑induced cognitive impairment.
Insights
Sevoflurane anesthesia impairs spatial memory in rats by increasing microRNA-188-3p. Inhibiting this microRNA or targeting the miR-188-3p-MDM2-p53 pathway may treat sevoflurane-induced cognitive dysfunction.
Area of Science:
- Neuroscience
- Anesthesiology
- Molecular Biology
Background:
- Sevoflurane is a widely used inhalation anesthetic.
- Sevoflurane-induced neuroapoptosis and cognitive deficits are reported in animals, but mechanisms are unclear.
- Understanding these mechanisms is crucial for patient safety and developing interventions.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying sevoflurane-induced cognitive impairment.
- To investigate the role of microRNA-188-3p (miR-188-3p) in sevoflurane's effects.
- To identify potential therapeutic targets for sevoflurane-induced cognitive dysfunction.
Main Methods:
- Morris water maze test to assess spatial memory in rats.
- Quantitative polymerase chain reaction and Western blot to measure gene and protein expression.
- Luciferase assays to confirm microRNA targeting.
- Inhibition of miR-188-3p and p53 activity.
Main Results:
- Sevoflurane anesthesia induced spatial memory impairments in rats.
- Sevoflurane significantly increased miR-188-3p expression.
- Inhibition of miR-188-3p attenuated cognitive deficits and neuroapoptosis.
- miR-188-3p targets MDM2, regulating the MDM2-p53 pathway.
- The miR-188-3p-MDM2-p53 axis plays a critical role in sevoflurane-induced cognitive dysfunction.
Conclusions:
- The miR-188-3p-MDM2-p53 signaling pathway is implicated in sevoflurane-induced cognitive impairment.
- miR-188-3p may serve as a potential therapeutic target for mitigating sevoflurane's adverse cognitive effects.
- Further research into this pathway could lead to novel neuroprotective strategies in anesthesia.
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