Effects and mechanisms of probucol on aging-related hippocampus-dependent cognitive impairment.
Effects and mechanisms of probucol on aging-related hippocampus-dependent cognitive impairment.
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DOI：
10.1016/j.biopha.2021.112266
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
Yaru Xie;A. Song;Yuting Zhu;Anni Jiang;Wenpeng Peng;Chun Zhang;Xianfang Meng
中科院分区：
文献类型：
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作者：
Yaru Xie;A. Song;Yuting Zhu;Anni Jiang;Wenpeng Peng;Chun Zhang;Xianfang Meng
本研究旨在观察普罗布考对衰老相关的海马依赖性认知功能障碍的影响，并探讨其可能的机制。方法采用D-半乳糖（100 mg/kg，每日1次，连续6周）皮下注射诱导小鼠衰老。然后每天一次给小鼠施用普罗布考或载体，持续2周。采用Morris水迷宫测验、新物体再认测验、情境恐惧条件化测验对受试者的校园相关认知进行评价。此外，突触可塑性进行了评估，RNA测序应用于进一步探讨的分子mechanism.ResultsAging D-半乳糖诱导的小鼠表现出明显的学习和记忆障碍，这是显着改善普罗布考。普罗布考可增加衰老小鼠海马棘密度和树突分支，增强长时程增强，增加PSD 95的表达。与D-半乳糖组相比，普罗布考调节了70个差异表达基因，其中38个基因上调，32个基因下调。最后，RNA测序结果进行了验证，通过定量逆转录-聚合酶链反应。结论普罗布考通过增强突触可塑性和调节基因表达，改善衰老小鼠的学习和记忆，表明普罗布考的潜在应用，以预防和治疗衰老相关疾病。
BackgroundIn the present study, we aimed to investigate the effects of probucol on aging-related hippocampus-dependent cognitive impairment and explore the potential mechanisms.MethodsD-galactose (100 mg/kg, once daily for 6 weeks) was subcutaneously injected to induce aging in mice. Then the mice were administered with probucol or vehicle once a day for 2 weeks. The hippocampus-related cognition was evaluated with Morris water maze test, novel object recognition test, and contextual fear conditioning test. Moreover, synaptic plasticity was assessed, and RNA-sequencing was applied to further explore the molecular mechanisms.ResultsAging mice induced byD-galactose showed conspicuous learning and memory impairment, which was significantly ameliorated by probucol. Meanwhile, probucol enhanced the spine density and dendritic branches, improved long-term potentiation, and increased the expression of PSD95 of aging mice. Probucol regulated 70 differentially expressed genes compared toD-galactose group, of which 38 genes were upregulated and 32 genes were downregulated. At last, RNA-sequencing results were verified by quantitative reverse transcription-polymerase chain reaction.ConclusionsProbucol improved learning and memory in aging mice through enhancing synaptic plasticity and regulating gene expression, indicating the potential application of probucol to prevent and treat aging-related disorders.