title: Neuroprotective effect of miR-665 against sevoflurane anesthesia-induced cognitive dysfunction in rats through PI3K/Akt signaling pathway by targeting insulin-like growth factor 2.
abstract: The aim of this study was to investigate thein vivoandin vitroeffects of miR-665 on sevoflurane anesthesia-induced cognitive dysfunction. SH-SY5Y cells and male SD rats were treated with sevoflurane to simulate anesthesia-induced cognitive dysfunction. The cells and rats both were transfected with a miR-665 mimic, inhibitor, scramble, IGF-2 siRNA, or treated with P13K/Akt inhibitor LY294002. The cell apoptosis, autophagy, growth related proteins, and mRNA levels were measured using different methods. The motor performance was assessed using the Morris water maze (MWM) test. Finally, the differences were statistically analyzed. It was noted that sevoflurane-induced miR-665 downregulation accompanied with the upregulation of IGF-2in vivoand motor deficitsin vitro. Moreover, sevoflurane also induced hippocampal neuroapoptosis; reduced regular autophagy; increased Bax/Bcl-2 ratio; decreased the expression of Beclin 1, PSD95, and p-CREB; and activated P13K/Akt signaling pathway. However, the treatment by miR-665 mimics significantly reversed all the molecular changes and improved motor performance. Our data demonstrate the neuroprotective effect of miR-665 against sevoflurane anesthesia-induced cognitive impairment. This study suggests that miR-665 might be explored as a potential target of therapy for sevoflurane-induced cognitive impairment.
authors.affiliation: Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Anesthesiology Zhengzhou 450003, Henan, China.
authors.forename: Xihua
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Anesthesiology Zhengzhou 450003, Henan, China.
authors.forename: Shuaiguo
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Anesthesiology Zhengzhou 450003, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Anesthesiology Zhengzhou 450003, Henan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Anesthesiology Zhengzhou 450003, Henan, China.
authors.forename: Gensheng
authors.initials: G
authors.lastname: Wang
keywords: P13k/Akt; insulin-like growth factor 2; miR-665; neuron apoptosis