Increased Notch2/NF-κB Signaling May Mediate the Depression Susceptibility: Evidence from Chronic Social Defeat Stress Mice and WKY Rats
Increased Notch2/NF-κB Signaling May Mediate the Depression Susceptibility: Evidence from Chronic Social Defeat Stress Mice and WKY Rats
复制标题
Notch2/NF-κB 信号传导的增加可能会调节抑郁易感性：来自慢性社交失败应激小鼠和 WKY 大鼠的证据
DOI：
10.1016/j.physbeh.2020.113197
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发表时间：
2021-01-01
影响因子：
2.9
通讯作者：
Chen, Xiaochun
中科院分区：
文献类型：
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作者：
Liao, Jiangfeng;Zeng, Guirong;Chen, Xiaochun
抑郁症的易感性被归因于慢性应激和遗传因素，但仍然未能确定明确的生物标志物。本研究旨在探讨慢性社会失败应激（CSDS）小鼠和Wistar京都（WKY）大鼠内侧前额叶皮质中Notch信号中断的作用。RNA测序和实时荧光定量PCR分析证实Notch信号通路参与抑郁症。Western blotting结果显示，与正常组和恢复组相比，易感组小鼠Notch 2和NF-κ B水平升高，Hes 1和Bcl 2/Bax比值降低;与Wistar组和非抑郁组相比，抑郁组WKY大鼠Notch 2和NF-κ B水平升高，Hes 1和Bcl 2/Bax比值降低。进一步分析表明，上述变化与抑郁样行为显著相关，Notch 2的表达与NF-κ B B的上调密切相关，而与Hes 1或Bcl 2/Bax比值的下调无关。总之，内侧前额叶皮质中增加的Notch 2/NF-κ B信号可能介导抑郁症易感性，为治疗重度抑郁症提供潜在的诊断生物标志物或治疗靶点。
The susceptibility to depression has been attributed to the chronic stress and genetic factors but still fails to identify definite biomarkers. The present study aimed to investigate the role of disrupted Notch signaling in the medial prefrontal cortex of the chronic social defeat stress (CSDS) mice and Wistar Kyoto (WKY) rats. RNA-sequencing and quantitative real-time PCR analyses evidenced the involvement of Notch signaling pathway in depression. Western blotting reported an increased level of Notch2 and NF-kappa B and a decreased level of Hes1 and Bcl2/Bax ratio both in the susceptible mice when compared with the control or resilient ones and in the depression WKY rats when compared with the Wistar or non-depression WKY groups. Further analysis showed that the above-mentioned changes were significantly correlated with the depression-like behaviors and that the elicited Notch2 strongly correlated with the upregulated NF-kappa B, not with the downregulated Hes1 or Bcl2/Bax ratio. In conclusion, the increased Notch2/NF-kappa B signaling in the medial prefrontal cortex may mediate depression susceptibility, providing a potential diagnostic biomarker or therapeutic target for treating major depressive disorder.