Merlo Sara, Spampinato Simona Federica, Capani Francisco, Sortino Maria Angela
Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, School of Medicine, Via S. Sofia 64, 95125 Catania, Italy.
Curr Alzheimer Res. 2016;13(6):631-40. doi: 10.2174/1567205013666160125113509.
In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid β (25-35) peptide (Aβ, 2 μM) to analyze the time-related effects of 17-β estradiol (17β-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17β-E2 24 h prior to, together with or 48 h after exposure to Aβ. This effect is mimicked by selective ERα agonist PPT (100 nM). Treatment with Aβ leads to early and transient (16-72 h) increase of pre- and post-synaptic proteins synaptophysin and PSD95, followed by a decrease coincident with neuronal death (7d), all prevented by 17β-E2. At 72 h of Aβ exposure, synaptic activity is increased, as by higher levels of glutamate and increased loading and unloading of FM 1-43-labeled synaptic vesicles. All these effects are also prevented by 17β-E2. These data point out beneficial effects of estrogen on early Aβ-induced synaptic disruption.
在本研究中，我们通过将海马脑片培养物暴露于低浓度的β-淀粉样蛋白（25-35）肽（Aβ，2 μM）来建立神经元损伤缓慢进展的模型，以分析17-β雌二醇（17β-E2，10 nM）的时间相关效应。神经元死亡在7天后发生，在暴露于Aβ之前24小时、同时或之后48小时添加17β-E2可预防神经元死亡。选择性雌激素受体α激动剂PPT（100 nM）可模拟这种效应。用Aβ处理导致突触前和突触后蛋白突触素和PSD95早期短暂（16-72小时）增加，随后与神经元死亡（7天）同时出现减少，所有这些均被17β-E2预防。在Aβ暴露72小时时，突触活性增加，如谷氨酸水平升高以及FM 1-43标记的突触小泡的装载和卸载增加。所有这些效应也被17β-E2预防。这些数据指出了雌激素对早期Aβ诱导的突触破坏的有益作用。
