AMPAkine CX516 alleviated chronic ethanol exposure-induced neurodegeneration and depressive-like behavior in mice

  • Toxicol Appl Pharmacol. 2022 Mar 15;439:115924. doi: 10.1016/j.taap.2022.115924.
Hui Yao  1 ,  Dalin Zhang  2 ,  Hao Yu  1 ,  Hui Shen  1 ,  Xinze Lan  1 ,  Hao Liu  1 ,  Xiaohuan Chen  1 ,  Xu Wu  1 ,  Guohua Zhang  3 ,  Xiaolong Wang  4
Affiliations
  • 1. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, PR China.
  • 2. Department of Thyroid Surgery, the 1st Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, PR China.
  • 3. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, PR China. Electronic address: [email protected].
  • 4. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, PR China. Electronic address: [email protected].
PMID: 35181401 DOI: 10.1016/j.taap.2022.115924
Abstract

Chronic ethanol exposure (CEE) is associated with greater neurodegenerative effects and an increased risk of depression disorder. The AMPAR is thought to be involved in depression and a reduction in its GluA1 subunit was observed in the mouse hippocampus after CEE. AMPAkines are positive allosteric modulators of the AMPA Receptor and have improved depressive-like behavior. However, the role of AMPARs in CEE-induced depressive-like behavior is not clear. It is unclear whether AMPAkines, positive allosteric agonists of AMPARs, protect against ethanol-induced depression. We investigated the effects of CX516 on ethanol-induced depressive-like behavior in a mouse model. CX516 (5 mg/kg) administration alleviated 20% (m/V) ethanol-induced depressive-like behavior in mice. Furthermore, CX516 significantly diminished the inhibition of the ERK1/2-BDNF-TrkB pathway in the hippocampus of ethanol-exposed mice. In addition, CX516 attenuated the levels of pro-inflammatory (IL-6, IL-1β), Apoptosis (Bax, Bcl-2), and neurodegeneration (FJC) in the mouse hippocampus induced by CEE.

Keywords
AMPA receptor; CX516; Depression; Ethanol; Neurodegeneration.
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