Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2
Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2
复制标题
硫化氢改善 APP/PS1 转基因小鼠的学习记忆障碍：一种由 Nrf2 激活介导的新机制。
DOI：
10.1016/j.pbb.2016.11.002
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发表时间：
2016-11-01
影响因子：
3.6
通讯作者：
Gong, Qihai
中科院分区：
文献类型：
--
作者：
Liu, Yuangui;Deng, Yuanyuan;Gong, Qihai
β-淀粉样蛋白（A β）斑块和氧化应激与阿尔茨海默病（AD）的发病机制有关。硫化氢（H2S）被认为是一种细胞保护剂，可改善记忆障碍，并在神经退行性疾病（包括AD）中发挥抗氧化作用。该实验旨在探索H2S对认知缺陷，A β水平和可能的抗氧化机制的影响。在此，APP/PS1转基因小鼠被注射硫氢化钠（NaHS，H2S供体，2.8 mg/kg），每天一次，持续三个月。结果发现，APP/PS 1转基因小鼠出现认知功能障碍，出现大量老年斑，沿着神经元减少，A β增加。然而，腹膜内（i. p.）注射NaHS可改善学习记忆障碍，减少老年斑数量，降低A β（1-40）和A β（1-42）水平，抑制神经元丢失，同时上调胱硫醚-β-合成酶（CBS）和3-巯基丙酮酸-硫转移酶（3 MST）水平。此外，β-淀粉样蛋白前体（APP）和β-分泌酶1（BACE 1）的蛋白水平显着抑制后，H2S的管理。此外，H2S通过上调核因子红细胞2相关因子2（Nrf 2）、血红素加氧酶-1（HO-1）和谷胱甘肽S-转移酶（GST）发挥抗氧化作用。这些结果表明，H2S可能通过抑制A β的产生和激活Nrf 2/抗氧化反应元件（ARE）通路，改善APP/PS1小鼠的学习记忆障碍，减少老年斑的数量。(C)2016爱思唯尔公司保留所有权利。
Beta-amyloid (A beta) plaques and oxidative stress are associated with the pathogenesis of Alzheimer's disease (AD). Hydrogen sulfide (H2S) has been recognized as a cytoprotectant, which improves teaming memory-impairment and exerts antioxidant effects in neurodegenerative disorders, including AD. The experiment was projected to explore the effects of H2S on cognitive deficits, A beta levels and possible antioxidant mechanisms. Here, APP/PS1 transgenic mice were injected sodium hydrosulfide (NaHS, a H2S donor, 2.8 mg/kg) once a day for three months. It was found that APP/PS1 transgenic mice exhibited cognitive deficits and a large number of senile plaques, along with neurons decrease and A beta increase. However, intraperitoneal (i.p.) injection of NaHS improved learning memory deficits, decreased the number of senile plaques, A beta(1-40) and A beta(1-42) levels, suppressed neurons loss, together with up-regulated the levels of cystathionine-beta-synthase (CBS) and 3-mercaptopyruvate-sulfurtransferase (3MST). Furthermore, the protein levels of beta-amyloid precursor (APP) and beta-secretase 1 (BACE1) were dramatically restrained after administration of H2S. In addition, H2S exerted antioxidant effects via up-regulation nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and glutathione S-transferase (GST). Taken together, these findings suggest that H2S ameliorates learning memory impairment, decreases the number of senile plaques in APP/PS1 mice possibly through inhibition of A beta production and activation of Nrf2/antioxidant response element (ARE) pathway. (C) 2016 Elsevier Inc All rights reserved.