Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation
Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation
复制标题
三七茎叶皂苷可对抗睡眠剥夺所致认知障碍小鼠海马神经元异常自噬和凋亡
DOI：
10.1016/j.jgr.2019.01.009
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发表时间：
2020-05-01
影响因子：
6.3
通讯作者：
Wang, Zhengtao
中科院分区：
文献类型：
--
作者：
Cao, Yin;Yang, Yingbo;Wang, Zhengtao
背景：睡眠剥夺（SD）通过在分子和细胞水平上抑制海马功能而损害学习和记忆。异常的自噬和凋亡与中枢神经系统的神经退行性疾病密切相关。本研究旨在探讨三七茎叶皂苷（SLSP）对SD所致学习记忆障碍小鼠海马异常神经元自噬和凋亡的缓解作用及其分子机制。方法：采用Morris水迷宫实验评估小鼠空间学习记忆。尼氏染色观察神经元形态变化。通过透射电子显微镜、免疫荧光染色、吖啶橙染色和tf-LC3质粒瞬时转染来检查自噬体的形成。 PI/annexin V 染色后通过流式细胞术分析细胞凋亡事件。 Western blotting检测自噬和凋亡相关蛋白的表达或激活。结果：SD 48 h后，SLSP可改善小鼠的空间学习记忆，抑制过度的自噬和细胞凋亡，同时增强海马神经元磷酸肌醇3激酶/蛋白激酶B/雷帕霉素信号通路哺乳动物靶标的激活。同时，它改善了海马神经细胞HT-22细胞中雷帕霉素诱导的异常自噬和凋亡，并重新激活了雷帕霉素信号转导的磷酸肌醇3-激酶/Alt/哺乳动物靶标。结论：SLSP可以减轻SD引起的认知障碍，这可能是通过抑制海马神经元异常自噬和凋亡来实现的。这些发现可能有助于 SLSP 在预防或治疗与 SD 相关的神经系统疾病中的临床应用。 (C) 2019 年韩国人参学会。 Elsevier B.V. 的出版服务
Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem-leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD.Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay.Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Alt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line.Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD. (C) 2019 The Korean Society of Ginseng. Publishing services by Elsevier B.V.