Lithium chloride reduced the level of oxidative stress in brains and serums of APP/PS1 double transgenic mice via the regulation of GSK3β/Nrf2/HO-1 pathway

Abstract

Aim: The aim of this study is to investigate whether lithium chloride (LiCl) can regulate glycogen synthase kinase-3β (GSK3β)/nuclear factor E2 related factor（Nrf2）/heme oxygenase-1 (HO-1) pathway to reduce the injury of oxidative stress in APP/PS1 double transgenic mice.

Materials and Methods: The APP/PS1 double transgenic and wild-type (WT) mice were divided randomly into four groups, i.e. WT, WT + LiCl (LiCl 100 mg/kg by gavage once daily), the transgenic + LiCl and the transgenic groups. The expressions of phosphor-GSK3β (ser9), Nrf2 and HO-1 at protein levels were detected by Western blotting. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) were measured by related detection kits. Nissl bodies in different brain regions were examined by Nissl staining.

Results: The decreased protein levels of phosphor-GSK3β (ser9), Nrf2 and HO-1, the declined activities of SOD and GSH-Px, the increased content of MDA and the decreased Nissl bodies in neurons were observed in the brains or serums of APP/PS1 mice as compared with WT. The treatment with LiCl attenuated these changes in the levels of GSK3β/Nrf2/HO-1 pathway and oxidative stress as well as Nissl bodies induced by APP/PS1 mutation.

Conclusion: LiCl reversed the declined activities of SOD and GSH-Px and the increased content of MDA as well as the decreased Nissl bodies in neurons in the brains or serums of APP/PS1 mice, the mechanism of which may be involved in the down-regulation of the activity of GSK3β and consequently enhances the expressions of Nrf2 and HO-1.

Keywords:

• Alzheimer’s disease
• APP/PS1 mice
• GSK3β/Nrf2/HO-1 pathway
• LiCl
• oxidative stress

Ethics approval and consent to participate

All experiments described here were preapproved by the Ethical Committee of Guizhou Medical University, China (No. 1702110).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financed by grants from the Natural Science Foundation of China (81760571), and the Foundation of Guizhou Province of China (2014-06, 2014-6008, 2016-4001).