miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1.PURPOSE
 Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain.  miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment.  However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear.


 C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days.  miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure.  Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis.  The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining.  The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis.


 Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment.  miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons.  Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons.  Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects.


 CONCLUSION
 miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.
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miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1.PURPOSE
 Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment.  miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.
miR-34a Inhibitor