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Apelin attenuates streptozotocin-induced learning and memory impairment by modulating necroptosis signaling pathway.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.intimp.2020.106546
Behzad Nasseri 1 , Parvin Zareian 1 , Hadi Alizade 2
Affiliation  

Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.



中文翻译:


Apelin 通过调节坏死性凋亡信号通路来减轻链脲佐菌素引起的学习和记忆障碍。



Apelin 是一种神经肽,在神经元保护中发挥重要作用。在这项研究中,我们研究了 apelin 脑室内给药对注射链脲佐菌素 (STZ) 的大鼠的空间学习和记忆相关行为以及海马坏死性凋亡信号通路的影响。 STZ 诱发痴呆后进行 Apelin 治疗 15 天。进行行为测试(莫里斯水迷宫)后,检查细胞和分子方面,以检测 apelin 对坏死性凋亡信号通路的影响。我们证明 STZ 管理显着降低了学习能力。然而,apelin 治疗显着逆转了这种神经炎症引起的行为障碍。此外,分子研究表明 apelin 治疗降低了海马 RIP1、RIP3 和 TNF-α 水平。我们的结果表明 apelin 治疗可减轻 STZ 诱发的痴呆。这种作用可能是通过抑制坏死性凋亡信号通路来介导的,该信号通路似乎与 apelin 降低中枢 TNF-α 水平的能力有关。该数据提供了 apelin 对 STZ 引起的学习和记忆障碍的神经保护作用的证据,并描述了一些潜在机制的特征。

更新日期:2020-05-12
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