Inhibition of xCT by sulfasalazine alleviates the depression-like behavior of adult male mice subjected to maternal separation stress

被引:0
作者
Wang, Shengwen [1 ]
Liu, Ye [3 ,4 ,5 ,6 ]
Wu, Zekang [1 ]
Jin, Yuwen [1 ]
Zhang, Tao [2 ]
Yang, Zhuo [1 ]
Liu, Chunhua [1 ]
机构
[1] Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China
[2] Nankai Univ, Coll Life Sci, 94 Weijin Rd, Tianjin 300071, Peoples R China
[3] Tianjin Key Lab Injuries Variat & Regenerat Nervou, Tianjin 300052, Peoples R China
[4] Minist Educ, Key Lab Posttrauma Neurorepair & Regenerat Cent Ne, Tianjin 300052, Peoples R China
[5] Tianjin Neurol Inst, Tianjin 300052, Peoples R China
[6] Tianjin Med Univ, Dept Neurol, Gen Hosp, Tianjin 300052, Peoples R China
基金
中国国家自然科学基金;
关键词
Maternal separation; Depression; XCT; Microglia; Glutamate; SYNAPTIC PLASTICITY; SYSTEM X(C)(-); HIPPOCAMPUS; RECEPTORS; NEUROINFLAMMATION; TRANSPORTER; EXPRESSION; ANXIETY; CELLS; MODEL;
D O I
10.1016/j.bbr.2023.114559
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Maternal separation (MS) can induce emotional disorders. Our previous study reported that MS resulted in depression-like behavior. In this study, we aimed to explore the role of xCT in depression-like behavior in adult mice subjected to MS stress. Pups were divided into the control group, the control + sulfasalazine (SSZ, 75 mg/ kg/day, i.p.) group, the MS group, and the MS+SSZ group. After MS, all pups were raised until PD60. Then, the depression-like behavior was detected by the novelty suppressed feeding (NSF) test, the forced swimming test (FST), and the tail suspension test (TST). The synaptic plasticity was examined by electrophysiological recordings and molecular biotechnology. The data showed that, compared with the control group, the mice in the MS group presented depression-like behavior, impairment of long-term potentiation (LTP), a reduction in the number of astrocytes, and activation of the microglia. Moreover, the expression of xCT was increased in the prefrontal cortex of MS mice, the EAAT2 and the Group II metabotropic glutamate receptors (mGluR2/3) were decreased, and the level of pro-inflammatory factors was increased in the prefrontal cortex. After the administration with SSZ, the depression-like behavior and the impairment of LTP were alleviated, the number of astrocytes was increased, and the microglial activation was inhibited. Moreover, the levels of EAAT2 and mGluR2/3 were ameliorated, the over-activation of the microglia was mitigated, and the levels of glutamate and proinflammatory factors were decreased. In conclusion, the inhibition of xCT by SSZ could alleviate depressionlike behavior partly via modulating the homeostasis of the glutamate system and dampening neuroinflammation.
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页数:12
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