Protective effect of melatonin on soluble Aβ1-42-induced memory impairment, astrogliosis, and synaptic dysfunction via the Musashi1/Notch1/Hes1 signaling pathway in the rat hippocampus.
Protective effect of melatonin on soluble Aβ1-42-induced memory impairment, astrogliosis, and synaptic dysfunction via the Musashi1/Notch1/Hes1 signaling pathway in the rat hippocampus.
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褪黑激素通过大鼠海马 Musashi1/Notch1/Hes1 信号通路对可溶性 Aβ1â42 诱导的记忆损伤、星形胶质细胞增生和突触功能障碍的保护作用
DOI：
10.1186/s13195-016-0206-x
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发表时间：
2016-09-15
期刊：
影响因子：
--
通讯作者：
Bi J
中科院分区：
文献类型：
--
作者：
Zhang S;Wang P;Ren L;Hu C;Bi J
β淀粉样蛋白（Aβ）在阿尔茨海默病（AD）发病机制中起关键作用，可溶性Aβ寡聚体比Aβ原纤维具有更强的细胞毒性。最近的证据表明，Notch信号受到AD和其他脑部疾病的影响。褪黑激素在AD的许多方面发挥有益的作用，并可能通过Notch 1信号调节来保护心肌缺血。因此，我们假设Notch 1信号通路参与褪黑素对可溶性Aβ1-42的神经保护作用。通过脑室内重复注射可溶性Aβ1-42建立AD大鼠模型。在Aβ1-42给药前24小时通过腹膜内注射给予褪黑激素治疗。研究了褪黑素对空间学习记忆、突触可塑性和星形胶质细胞增生的影响。使用免疫组织化学、蛋白质印迹和定量实时PCR检测几种Notch 1信号传导组分的表达，包括Notch 1、Notch 1胞内结构域（NICD）、Hairy和分裂增强子1（Hes 1，Notch的下游效应子）和Musashi 1（Notch的正调节子）。进行了体外研究，以确定褪黑激素介导的抗Aβ1-42保护作用是否被DAPT（一种Notch信号传导抑制剂）抑制。褪黑素改善了Aβ1-42诱导的空间学习和记忆障碍，减轻了突触功能障碍，并减少了星形胶质细胞增生。褪黑激素还改善了Aβ1-42对Notch 1、NICD、Hes 1和Musashi 1的作用。体外研究表明，DAPT可有效阻断褪黑素对Aβ1-42的神经保护作用。这些结果表明，褪黑素可能通过Musashi 1/Notch 1/Hes 1信号通路改善可溶性Aβ1-42诱导的空间学习记忆障碍、突触可塑性和星形胶质细胞增生。
Amyloid-beta (Aβ) plays a key role in Alzheimer’s disease (AD) pathogenesis, and soluble Aβ oligomers are more cytotoxic than Aβ fibrils. Recent evidence suggests that Notch signaling is affected by AD and other brain diseases. Melatonin exerts beneficial effects on many aspects of AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1–42. An AD rat model was established via repeated intracerebroventricular administration of soluble Aβ1–42. Melatonin treatment was administered 24 hours prior to Aβ1–42 administration via an intraperitoneal injection. The effects of melatonin on spatial learning and memory, synaptic plasticity, and astrogliosis were investigated. The expression of several Notch1 signaling components, including Notch1, the Notch1 intracellular domain (NICD), Hairy and enhancer of split 1 (Hes1, a downstream effector of Notch), and Musashi1 (a positive regulator of Notch), were examined using immunohistochemistry, western blotting, and quantitative real-time PCR. In vitro studies were conducted to determine whether the melatonin-mediated protection against Aβ1–42 was inhibited by DAPT, an inhibitor of Notch signaling. Melatonin improved the Aβ1–42-induced impairment in spatial learning and memory, attenuated synaptic dysfunction, and reduced astrogliosis. Melatonin also ameliorated the effects of Aβ1–42 on Notch1, NICD, Hes1, and Musashi1. The in vitro studies demonstrated that DAPT effectively blocked the neuroprotective effect of melatonin against Aβ1–42. These findings suggest that melatonin may improve the soluble Aβ1–42-induced impairment of spatial learning and memory, synaptic plasticity, and astrogliosis via the Musashi1/Notch1/Hes1 signaling pathway.
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影响因子：
168.9
作者：
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