The neuroprotective effect of LCZ696 on methamphetamine-induced cognitive impairment in mice.

Abstract

OBJECTIVE:

Methamphetamine (METH) exposure commonly causes cognitive impairment. An angiotensin II receptor/neprilysin inhibitor (ARNI), LCZ696 has been demonstrated to inhibit inflammation, oxidative stress and apoptosis. The present study was designed to examine the effect of LCZ696 on METH-induced cognitive impairment and the underlying mechanism.

METHODS:

Following daily treatment of either saline or METH (5 mg/kg) for 5 consecutive days, the cognitive function was tested using the Y-maze and the Novel Object Recognition (NOR) in Experiment 1. In Experiment 2, mice were initially treated with saline or LCZ696 (60 mg/kg) for 9 consecutive days, followed by LCZ696, METH or saline for 5 days. Cognitive testing was carried out as Experiment 1. In Experiment 3, SH-SY5Y cells were treated with either METH (2.5 Mm) or ddH2O for 12 h. The apoptosis and reactive oxygen species (ROS) level of SH-SY5Y were examined. In Experiment 4, SH-SY5Y cells were pretreated with either ddH2O or LCZ696 (70um) for 30 min, followed by ddH2O or METH treatment for 12 h. Nrf2 and HO-1 protein expression was examined in the ventral tegemental area (VTA) of all the animals and SH-SY5Y cells.

RESULTS:

LCZ696 significantly improved METH-induced cognitive impairment, in conjunction with decreased apoptosis and ROS levels in VTA of METH-treated mice and SH-SY5Y cells. METH significantly decreased Nrf2 and HO-1 protein expression in VTA of mice and SH-SY5Y cells, which was reversed by LCZ696 treatment.

CONCLUSION:

LCZ696 yields a neuroprotective effect against METH-induced cognitive dysfunction via the Nrf2/HO-1 signaling pathway.

• Authors: Liyin Qian, Yuer Ruan, Xinshuang Gong, Zhaoying Yu, Shujun Lin, Xiaofang Li, Yao Shen, Hu Luo, Zizhen Si, Yu Liu
• Journal: Neuroscience letters (Neurosci Lett) Vol. 823 Pg. 137630 (Feb 16 2024) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 38215873 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier B.V. All rights reserved.

Chemical References

• Methamphetamine
• Neuroprotective Agents
• sacubitril and valsartan sodium hydrate drug combination
• Reactive Oxygen Species
• NF-E2-Related Factor 2
• Valsartan
• Aminobutyrates
• Biphenyl Compounds
• Drug Combinations

Topics

• Animals
• Humans
• Methamphetamine (toxicity)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• NF-E2-Related Factor 2
• Cell Line, Tumor
• Neuroblastoma (metabolism)
• Cognitive Dysfunction (chemically induced, drug therapy)
• Apoptosis
• Valsartan
• Aminobutyrates
• Biphenyl Compounds
• Drug Combinations