MK-801对皮质酮诱导抑郁样行为大鼠海马mBDNF和proBDNF表达的影响

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1097-1102.

MK-801对皮质酮诱导抑郁样行为大鼠海马mBDNF和proBDNF表达的影响

李建国^1*, 王颖¹, 李玥天², 燕子¹, 赵欣¹, 张宇¹

1.山西医科大学生理学系细胞生理学教育部重点实验室,山西太原 030001;
2.四川大学华西口腔医学院,四川成都 610041

收稿日期:2020-11-19 修回日期:2021-04-30 出版日期:2021-08-05 发布日期:2021-07-21
通讯作者: *lijg@sxmu.edu.cn
基金资助:
国家自然科学基金(81671231);山西省回国留学人员基金(2017-056);山西省“1331工程”重点学科建设计划(XK201708)

MK-801 changes the expression of mBDNF and proBDNF in the hippocampus of rats with corticosterone-induced depression-like behavior

LI Jian-guo^1*, WANG Ying¹, LI Yue-tian², YAN Zi¹, ZHAO Xin¹, ZHANG Yu¹

1. Key Laboratory of Cellular Physiology Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan 030001;
2. West China School of Stomatology, Sichuan University, Chengdu 610041, China

Received:2020-11-19 Revised:2021-04-30 Online:2021-08-05 Published:2021-07-21
Contact: *lijg@sxmu.edu.cn

摘要/Abstract

摘要： 目的 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂通过脑源性神经营养因子(BDNF)发挥抗抑郁作用。然而,NMDA受体拮抗剂调控BDNF表达的机制尚不清楚。方法口服皮质酮(CORT)诱导大鼠抑郁样行为。采用高架十字迷宫实验、蔗糖偏好实验、旷场实验和强迫游泳实验观察动物的抑郁样行为,采用蛋白免疫印迹方法检测动物背侧和腹侧海马DG脑区成熟BDNF(mBDNF)和前体BDNF(proBDNF)的表达。结果慢性给予CORT诱发大鼠抑郁样行为。NMDA受体拮抗剂地佐环平(MK-801)可减轻动物抑郁样行为,增加大鼠背侧和腹侧海马DG脑区中mBDNF的表达,同时降低proBDNF的表达(P＜0.05)。组蛋白去乙酰化酶拮抗剂辛二酰苯胺异羟肟酸(SAHA)能够减轻动物抑郁样行为,增加海马脑区的mBDNF表达,降低proBDNF的表达(P＜0.05)。然而,预先给予MK-801后,SAHA对大鼠抑郁样行为、海马DG脑区的mBDNF和proBDNF表达都无显著的影响。结论 MK-801可通过组蛋白乙酰化改变大鼠海马DG区mBDNF和proBDNF的表达,发挥抗抑郁作用,这将为抗抑郁治疗提供新靶点。

关键词: MK-801, 脑源性神经营养因子, 抑郁症, 海马, 大鼠

Abstract: Objective N-methyl-D-aspartate (NMDA) receptor antagonist produces antidepressant effects through the brain-derived neurotrophic factor (BDNF). However, the mechanism of NMDA regulation of BDNF expression by receptor antagonist is unclear. Methods Corticosterone (CORT) was orally administrated to induce depressive-like behaviors in rats. Using elevated plus maze test, sucrose preference test, open field test, and forced swimming test to observe the depressive-like behaviors. Western blot was applied to analyze the expression of mature BDNF (mBDNF) and precursor (proBDNF) in the dorsal and ventral hippocampus dentate gyrus (DG). Results Chronic administration of CORT induced depressive-like behaviors in rats. Acute administration of NMDA receptor antagonist dizocilpine (MK-801) alleviated the depressive-like behaviors (P＜0.05). MK-801 increased the expression of mBDNF and decreased the expression of proBDNF in the dorsal and ventral hippocampus DG of rats(P＜0.05). Furthermore, administration of deacetylases antagonist suberoylanilide hydroxamic acid (SAHA) increased the mBDNF expression, decreased the proBDNF expression, and alleviated depressive-like behaviors in CORT-treated rats (P＜0.05). However, SAHA treatment after MK-801 showed no significant changes in the expression of mBDNF and proBDNF in the hippocampus DG of CORT-treated rats. Conclusions MK-801 can change the expression of mBDNF and proBDNF in the hippocampus DG through histone acetylation to play antidepressant effects, which suggest a potential target for antidepressant therapy.

Key words: MK-801, brain-derived neurotrophic factor, major depressive disorder, hippocampus, rat

中图分类号:

Q189

李建国, 王颖, 李玥天, 燕子, 赵欣, 张宇. MK-801对皮质酮诱导抑郁样行为大鼠海马mBDNF和proBDNF表达的影响[J]. 基础医学与临床, 2021, 41(8): 1097-1102.

LI Jian-guo, WANG Ying, LI Yue-tian, YAN Zi, ZHAO Xin, ZHANG Yu. MK-801 changes the expression of mBDNF and proBDNF in the hippocampus of rats with corticosterone-induced depression-like behavior[J]. Basic & Clinical Medicine, 2021, 41(8): 1097-1102.

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