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

Abstract

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

CLC Number:

Q189

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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