D-Serine produces antidepressant-like effects in mice through suppression of BDNF signaling pathway and regulation of synaptic adaptations in the nucleus accumbens.
D-Serine produces antidepressant-like effects in mice through suppression of BDNF signaling pathway and regulation of synaptic adaptations in the nucleus accumbens.
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d-丝氨酸通过抑制 BDNF 信号通路和调节伏隔核突触适应在小鼠中产生抗抑郁样作用
DOI：
10.1186/s10020-021-00389-x
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发表时间：
2021-10-15
期刊：
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Chen Z;Tang Z;Zou K;Huang Z;Liu L;Yang Y;Wang W
目的丝氨酸是中枢神经系统中N-甲基-d-天冬氨酸受体（NMDARs）的重要内源性共激动剂，可影响脑源性神经营养因子（BDNF）系统的功能，而BDNF系统在调节突触可塑性中起重要作用。本研究旨在系统研究d-丝氨酸在抑郁行为中的作用及其机制。方法采用慢性社会失败应激（CSDS）模型，采用高效液相色谱法（HPLC）测定d-丝氨酸在NAc中的含量。采用强迫游泳实验（FST）和悬尾实验（TST）观察d-丝氨酸的抗抑郁作用，并在CSDS模型上观察d-丝氨酸的抗抑郁作用。我们应用社会互动和蔗糖偏好测试来确定CSDS模型的敏感性。Western blotting检测CSDS和d-丝氨酸处理后NAc中BDNF信号通路的变化。BDNF信号抑制剂（K252 a）也被用于阐明d-丝氨酸的抗抑郁样机制。结果抑郁症易感小鼠NAc内d-丝氨酸浓度降低，在FST和TST实验中，NAc内注射d-丝氨酸具有抗抑郁样作用，而不影响小鼠的自主活动，d-丝氨酸对CSDS抑郁模型也有作用。此外，d-丝氨酸在CSDS过程中下调NAc中的BDNF信号通路。BDNF信号抑制剂K252 a可增强d-丝氨酸的抗抑郁作用。结论d-丝氨酸通过抑制BDNF信号通路和调节NAc突触可塑性发挥抗抑郁样作用。
Objectived-Serine is a crucial endogenous co-agonist of N-methyl-d-aspartate receptors (NMDARs) in the central nervous system and can affect the function of the brain derived neurotrophic factor (BDNF) system, which plays an essential role in modulating synaptic plasticity. The current study aimed to systematically evaluate the role and mechanisms ofd-serine in depressive behavior in nucleus accumbens (NAc).Methodsd-Serine concentration in the chronic social defeat stress (CSDS) model in NAc was measured using high-performance liquid chromatography (HPLC). The antidepressant-like effects ofd-serine were identified using forced swim test (FST) and tail suspension test (TST) in control mice and then assessed in CSDS model. We applied social interaction and sucrose preference tests to identify the susceptibility of CSDS model. Western blotting was further performed to assess the changes of BDNF signaling cascade in NAc after CSDS andd-serine treatment. The BDNF signaling inhibitor (K252a) was also used to clarify the antidepressant-like mechanism ofd-serine. Moreover,d-serine effects on synaptic plasticity in NAc were investigated using electrophysiological methods.Resultsd-Serine concentration was decreased in depression susceptible mice in NAc.d-Serine injections into NAc exhibited antidepressant-like effects in FST and TST without affecting the locomotor activity of mice.d-Serine was also effective in CSDS model of depression. Moreover,d-serine down-regulated the BDNF signaling pathway in NAc during CSDS procedure. Furthermore, BDNF signaling inhibitor (K252a) enhanced the antidepressant effects ofd-serine. We also found thatd-serine was essential for NMDARs-dependent long-term depression (LTD).Conclusiond-Serine exerts antidepressant-like effects in mice mediated through restraining the BDNF signaling pathway and regulating synaptic plasticity in NAc.
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慢性D链升高对抑郁症和焦虑相关行为动物模型的影响。
影响因子：
3.7
作者：
Otte DM;Barcena de Arellano ML;Bilkei-Gorzo A;Albayram O;Imbeault S;Jeung H;Alferink J;Zimmer A
通讯作者：
Zimmer A
影响因子：
16.6
作者：
Lorsch ZS;Loh YE;Purushothaman I;Walker DM;Parise EM;Salery M;Cahill ME;Hodes GE;Pfau ML;Kronman H;Hamilton PJ;Issler O;Labonté B;Symonds AE;Zucker M;Zhang TY;Meaney MJ;Russo SJ;Shen L;Bagot RC;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
4
作者：
Kowiański P;Lietzau G;Czuba E;Waśkow M;Steliga A;Moryś J
通讯作者：
Moryś J
影响因子：
4.4
作者：
Snyder, SH;Kim, PM
通讯作者：
Kim, PM
脑源性神经营养因子通过 TrkB/Akt/CREB 通路诱导 SH-SY5Y 细胞中硫氧还蛋白-1 的表达。
影响因子：
3.9
作者：
Bai, Liping;Zhang, Se;Bai, Jie
通讯作者：
Bai, Jie