Effects of tPA gene methylation / demethylation in Propofol protection of learning and memory function after electroshock therapy in depressive rats
ZHANG Fan1 ZHU Xianlin2
1.Department of Anesthesiology, the People′s Hospital of Jianyang City, Sichuan Province, Chengdu 641400, China;
2.Department of Anesthesiology, the Central Hospital of Enshi Autonomous Prefecture, Hubei Province, Enshi 445000, China
Abstract：Objective To investigate the protective effect of Propofol on learning and memory function in depressive rats after electroshock therapy (ECT) by regulating tissue plasminogen activator (tPA) gene methylation/demethylation. Methods Seventy-two adult male SD rats were used in this study and eighteen rats were randomly selected as the control group (group C). The remaining fifty-four rats were randomly divided into group D, group E and group F after depressive modeling, with 18 rats in each group. Group C was not given experimental treatment; group D was intraperitoneally injected with normal saline + pseudo-ECT; group E was intraperitoneally injected with normal saline + ECT; group F was intraperitoneally injected with Propofol + ECT. Depressive behavior and learning function of rats were measured by sucrose preference percentage (SPP), escape latency (EL) and space exploration time (SET). The mRNA levels of hippocampus tPA, DNA methyltransferase (DNMT) 1, DNMT3a, DNMT3b and ten-elevan translocation (TET) 1 were detected by reverse transcription PCR. The expressions of tPA and DNMT1 in hippocampus were detected by Western blot. MeDIP-qPCR was used to detect tPA methylation rate. After ECT treatment, compared with group D, SPP increased in Group E and F, EL prolonged and SET shortened in group E, tPA mRNA and protein expression in hippocampal CA1 area decreased, DNMT1 mRNA and protein expression increased, and tPA methylation rate increased, with statistically significant differences (all P ＜ 0.05). Compared with group E, in group F, EL shortened and SET prolonged, tPA mRNA and protein expression in hippocampal CA1 area increased, DNMT1 mRNA and protein expression decreased, and tPA methylation rate decreased (all P ＜ 0.05). There was no significant difference in mRNA expression of DNMT3a, DNMT3b and TET1 in each group (all P ＞ 0.05). Conclusion Propofol can effectively reduce ECT-induced learning and memory impairment in depressive rats. The mechanism may be related to the downregulate the expression of DNMT1 in the hippocampal CA1 region to reduce the methylation level of the tPA gene resulting in increase the expression level of tPA mRNA and protein.
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2020, Vol. 17 
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