Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process
Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process
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DOI：
10.1016/j.pnpbp.2018.10.005
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发表时间：
2019-03-08
影响因子：
5.6
通讯作者：
Zarrindast, Mohammad-Reza
中科院分区：
文献类型：
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作者：
Aminyavari, Samaneh;Zahmatkesh, Maryam;Zarrindast, Mohammad-Reza
阿尔茨海默病（Alzheimer's disease，AD）是一种进行性神经退行性疾病，自噬应激是导致淀粉样蛋白β（amyloid beta，A β）聚集和神经功能丧失的潜在原因。Apelin-13是一种调节细胞自噬的神经肽，对神经细胞损伤具有保护作用。我们研究了Apelin-13对A β诱导的记忆缺陷以及自噬和凋亡过程的影响。我们进行了双侧CA 1内注射A β 25-35单独或与爱帕琳-13组合。采用Morris水迷宫（MWM）和Y-迷宫测试评价空间参考和工作记忆。在A β注射后2、5、10和21天收获海马。使用蛋白质印迹技术评估轻链3（LC 3 II/I）比率、组蛋白脱乙酰酶6（HDAC 6）水平、Caspase-3切割和mTOR磷酸化。CA 1内注射A β导致工作记忆和空间记忆受损。我们在斐济治疗的动物中观察到更高的LC 3 II/I比率、裂解的半胱天冬酶-3和更低的HDAC 6和p-mTOR/mTOR比率。Apelin-13对A β对工作记忆和空间记忆的破坏性影响提供了显着的保护。在注射A β后第10天和第21天，爱帕琳-13阻止了LC 3 II/I比率的增加并裂解了半胱天冬酶-3。它还限制了A β诱导的HDAC 6表达减少。这意味着爱帕琳-13抑制了自噬和凋亡。我们的研究结果表明，Apelin-13的神经保护作用可能部分与自噬和凋亡抑制有关，通过mTOR信号通路。Apelin-13可能是改善记忆障碍的一种有前途的方法，并可能为AD的新治疗计划铺平道路。
Alzheimer's disease (AD) by progressive neurodegenerative pattern is associated with autophagy stress which is suggested as a potential cause of amyloid beta (A beta) aggregation and neural loss. Apelin-13, a neuropeptide with modulatory effect on autophagy, has been shown the beneficial effects on neural cell injuries. We investigated the effect of Apelin-13 on A beta-induced memory deficit as well as autophagy and apoptosis processes. We performed bilateral intra-CA1 injection of A beta 25-35 alone or in combination with Apelin-13. Spatial reference and working memory was evaluated using the Morris water maze (MWM) and Y-maze tests. Hippocampus was harvested on 2, 5, 10 and 21 days after A beta injection. The light chain 3 (LC3II/I) ratio, histone deacetylase 6 (HDAC6) level, Caspase-3 cleavage, and mTOR phosphorylation were assessed using western blot technique. Intra-CA1 injection of A beta caused impairment of working and spatial memory. We observed higher LC3II/I ratio, cleaved caspase-3 and lower HDAC6, and p-mTOR/mTOR ratio in Fiji-treated animals. Apelin-13 provided significant protection against the destructive effects of A beta on working and spatial memory. Apelin-13 prevented the increase of LC3II/I ratio and cleaved caspase-3 on days 10 and 21 after injection of A beta. It also limited the A beta-induced reduction in HDAC6 expression. This implies that Apelin-13 has suppressed both autophagy and apoptosis. Our findings suggested that the neuroprotection of Apelin-13 may be in part related to autophagy and apoptosis inhibition via the mTOR signaling pathway. Apelin-13 may be a promising approach to improve memory impairment and potentially pave the way for new therapeutic plans in AD.