BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress
BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress
复制标题
BDNF/TrkB 通路通过抑制海马 ER 应激介导 H2S 在 CUMS 暴露大鼠中的抗抑郁样作用
DOI：
10.1007/s12017-018-8489-7
复制
发表时间：
2018-04
影响因子：
3.5
通讯作者：
Xiao-Qing Tang
中科院分区：
文献类型：
--
作者：
Le Wei;Li-Yuan Kan;Hai-Ying Zeng;Yi-Yun Tang;Hong-Lin Huang;Ming Xie;Wei Zou;Chun-Yan Wang;Ping Zhang;Xiao-Qing Tang
我们以前的工作表明，硫化氢（H2S）显着减弱慢性不可预测的温和的压力（H2S）诱导的抑郁样行为和海马内质网（ER）的压力。脑源性神经营养因子（BDNF）通过其受体酪氨酸蛋白激酶B（Trk B）发挥抗抑郁样作用。我们以前发现，H2S上调BDNF和p-TrkB在海马中的表达，在CNS暴露的大鼠。因此，本研究探讨BDNF/TrkB通路是否通过阻断海马内质网应激介导H2S的抗抑郁样作用。我们发现，K252 a（BDNF/TrkB通路抑制剂）显著增加了H2S和NaHS联合处理大鼠强迫游泳和悬尾实验中的运动时间，并增加了新奇抑制摄食实验中的摄食潜伏期。类似地，K252 a逆转NaHS对CNS诱导的海马ER应激的保护作用，如ER应激相关蛋白、葡萄糖调节蛋白78、CCAAT/增强子结合蛋白同源蛋白和切割的caspase-12水平的增加所证明的。总之，我们的研究结果表明，BDNF/TrkB通路发挥了重要的介导作用，在抗抑郁剂样作用的H2S.in暴露的大鼠，这是通过抑制海马ER应激。这些数据提供了一个新的机制，保护H2S。对硫化氢诱导的抑郁样行为。
Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophicfactor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased themmobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversedthe protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved.caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S.in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S.against CUMS-induced depressive-like behaviors.
登录
查看更多内容
硫化氢通过上调 BDNF-TrkB 通路来保护海马免受慢性不可预测的轻度应激诱导的氧化应激
影响因子：
--
作者：
Hu M;Zou W;Wang CY;Chen X;Tan HY;Zeng HY;Zhang P;Gu HF;Tang XQ
通讯作者：
Tang XQ
硫化氢抑制 PC12 细胞中 MPP 诱导的醛应激和内质网应激：涉及 BDNF 的上调
影响因子：
3.7
作者：
Fan Xiao;Ping Zhang;Ai-Hua Chen;Chun-Yan Wang;Wei Zou;Hong-Feng Gu;Xiao-Qing Tang
通讯作者：
Xiao-Qing Tang
DOI：
10.1523/jneurosci.16-03-01066.1996
发表时间：
1996-02
期刊：
--
影响因子：
--
作者：
K. Abe;H. Kimura
通讯作者：
K. Abe;H. Kimura
影响因子：
22.4
作者：
Cummings, Colleen M.;Caporino, Nicole E.;Kendall, Philip C.
通讯作者：
Kendall, Philip C.
影响因子：
5.5
作者：
Lindholm D;Korhonen L;Eriksson O;Kõks S
通讯作者：
Kõks S