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

  • Behav Brain Res. 2022 Apr 29;424:113813. doi: 10.1016/j.bbr.2022.113813.
Hui Yao  1 ,  Wenting Guo  2 ,  Longlong Suo  2 ,  Guoliang Li  2 ,  Yunsheng Wang  2 ,  Yuanyuan Chen  2 ,  Yingui Sun  3 ,  Runtao Ding  4
Affiliations
  • 1. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, 110122, PR China; Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, PR China.
  • 2. Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, PR China.
  • 3. Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, PR China. Electronic address: [email protected].
  • 4. Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, PR China. Electronic address: [email protected].
PMID: 35202718 DOI: 10.1016/j.bbr.2022.113813
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.

Keywords
AMPA receptor; Depression; LPS; LY450108.
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