Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression.
Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression.
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淫羊藿苷调节抑郁症大鼠海马神经发生机制的探讨。
DOI：
10.4103/1673-5374.320993
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发表时间：
2022-03
影响因子：
6.1
通讯作者：
Wu LL
中科院分区：
文献类型：
--
作者：
Zeng NX;Li HZ;Wang HZ;Liu KG;Gong XY;Luo WL;Yan C;Wu LL
淫羊藿苷(ICA)对抑郁症和海马区损伤有显著的保护作用，但它不能有效地穿越血脑屏障并在脑内蓄积。因此，ICA保护抑郁症患者海马区损伤的机制尚不清楚。在这项研究中，我们对脑脊液进行蛋白质组学分析，以探讨ICA阻止抑郁症患者功能障碍的海马神经发生的机制。慢性轻度应激6周后，每天皮下注射ICA 120 mg/kg，建立大鼠抑郁模型。结果表明，ICA可减轻抑郁大鼠的抑郁症状、学习记忆功能障碍、神经发生功能障碍和海马齿状回神经元丢失。取大鼠胚胎海马区神经干细胞，在含20%脑脊液的培养液中培养，加入10 0μM皮质酮。ICA处理的大鼠脑脊液的加入在很大程度上阻止了皮质酮对神经元增殖和分化的抑制。通过对脑脊液的蛋白质组学分析，鉴定了52个受慢性不可预测的轻度应激和ICA调控的差异表达蛋白质。这些蛋白主要参与核糖体、PI3K-Akt信号通路和IL-17信号通路。平行反应监测质谱仪显示，Rps4x、Rps12、Rps14、Rps19、Hsp90b1和Hsp90aa1在慢性不可预测的轻度应激中上调，而在ICA中下调。相比之下，HtrA1在慢性不可预测的温和应激下表达下调，并被ICA上调。这些发现表明，ICA可以通过调节脑脊液中某些蛋白质的表达来预防抑郁和功能障碍的海马神经发生。该研究于2017年3月获得广州中医药大学实验动物伦理委员会中国的批复。
Icariin (ICA) has a significant capacity to protect against depression and hippocampal injury, but it cannot effectively cross the blood-brain barrier and accumulate in the brain. Therefore, the mechanism by which ICA protects against hippocampal injury in depression remains unclear. In this study, we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression. A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks, after which 120 mg/kg ICA was administered subcutaneously every day. The results showed that ICA alleviated depressive symptoms, learning and memory dysfunction, dysfunctional neurogenesis, and neuronal loss in the dentate gyrus of rats with depression. Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone. The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation. Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid. These proteins were mainly involved in the ribosome, PI3K-Akt signaling, and interleukin-17 signaling pathways. Parallel reaction monitoring mass spectrometry showed that Rps4x, Rps12, Rps14, Rps19, Hsp90b1, and Hsp90aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA. In contrast, HtrA1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA. These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid. The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.
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影响因子：
11.4
作者：
Lepko, Tjasa;Pusch, Melanie;Ninkovic, Jovica
通讯作者：
Ninkovic, Jovica
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
3.8
作者：
Nadeem, Ahmed;Ahmad, Sheikh F.;Attia, Sabry M.
通讯作者：
Attia, Sabry M.
慢性不可预测轻度应激抑郁大鼠行为、齿状回神经发生和海马miR-124表达的动态变化
影响因子：
6.1
作者：
Huang, Yun-Ling;Zeng, Ning-Xi;Wu, Li-Li
通讯作者：
Wu, Li-Li
影响因子：
5.4
作者：
Kim, Bo-Kyung;Park, Minhwa;Woo, So-Youn
通讯作者：
Woo, So-Youn