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

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

doi:10.1016/j.bbr.2022.113813

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. Epub 2022 Feb 22.

Authors

Hui Yao¹, Wenting Guo², Longlong Suo², Guoliang Li², Yunsheng Wang², Yuanyuan Chen², Yingui Sun³, Runtao Ding⁴

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: yinguisunsdpc@163.com.
⁴ Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, PR China. Electronic address: fydingrt@wfmc.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antidepressive Agents / pharmacology
Disease Models, Animal
Hippocampus / metabolism
Lipopolysaccharides* / pharmacology
Mice
Receptors, AMPA* / metabolism

Substances

Antidepressive Agents
Lipopolysaccharides
Receptors, AMPA