Preventive effects of the AMPA receptor potentiator LY450108 in an LPS-induced depressive mouse model

AMPA 受体增强剂 LY450108 对 LPS 诱发的抑郁小鼠模型的预防作用

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作者:Hui Yao, Wenting Guo, Longlong Suo, Guoliang Li, Yunsheng Wang, Yuanyuan Chen, Yingui Sun, Runtao Ding

Abstract

Previous studies have demonstrated a close association between α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) and depressive disorders, and activation of AMPARs may represent a promising way to treat depression. However, the effects of AMPAR potentiators on depression and the underlying mechanism have not been comprehensively clarified. We used lipopolysaccharide (LPS) to establish a depressive mouse model and an in vitro damage model of SH-SY5Y cells, and the AMPAR potentiator LY450108 was introduced to the study. We found that LY450108 alleviated LPS-induced depressive behavior and abnormal phosphorylation of hippocampal AMPARs in mice. LY450108 also alleviated LPS-induced apoptosis and decreased the viability of SH-SY5Y cells. In addition, LY450108 protected SH-SY5Y cells from LPS-induced abnormal phosphorylation of AMPARs. In conclusion, our findings suggest that LY450108 has antidepressant effects against LPS-induced neuronal damage and depression.

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