Regulation and Molecular Mechanism of Histone Acetylation Modification in Sevoflurane-induced POCD in Mice
Journal of King Saud University - Science(2020)
Abstract
Objective: The objective is to explore the effect of sevoflurane anesthesia on histone acetylation and the mechanism of learning and memory ability in mice, so as to provide reference for the development of drugs with cognitive protection and brain injury reduction. Method: In this study, 40 healthy male BALB/c mice are selected as the study subjects and randomly divided into four groups: control group (group A), sevoflurane group (group B), sevoflurane + SAHA group (group C) and SAHA group (group D). A postoperative cognitive dysfunction (POCD) model induced by sevoflurane is established. After extracting the hippocampus, Morris water maze test is used to detect the spatial learning and memory ability of mice, and conditioned fear test is used to detect conditioned fear memory ability. The expression of brain derived neural factor (BDNF) and synaptotagmin-1 (SYT-I) mRNA in hippocampus is detected by real-time fluorescence quantitative PCR. Western blotting is used to detect the expression of Acetylated histone-3 (Ac-H3), BDNF and SYT-I in mouse hippocampus. Results: After sevoflurane anesthesia, the escape latency of mice in Morris water maze experiment is significantly prolonged, and the target quadrant time ratio is significantly reduced. Compared with group A, the time ratio and times of stiffness in group B are significantly lower (P < 0.05). There is no significant difference between group C and group A (P > 0.05). The expression level of Ac-H3, BDNF and SYT-I protein in group B is significantly lower than that in group A (P < 0.05). Compared with group B, the expression level of Ac-H3, BDNF and SYT-I protein in group D is significantly higher, and the difference is statistically significant (P < 0.05), while the effect of sevoflurane anesthesia might be weakened by using the histone deacetylase inhibitor SAHA. Conclusion: Sevoflurane anesthesia can inhibit the expression of BDNF and SYT-I by inhibiting the acetylation of histone-3 in the hippocampus of mice, thus leading to POCD. (C) 2019 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.
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Key words
Histone deacetylase inhibitor,Sevoflurane,POCD,BDNF,Syt-I
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