Aims
Alzheimer's disease (AD) is the most common neurodegenerative disease, and all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. In this study, we hypothesized that glutamine (Gln) offers protection against oxidative stress injury in SAMP8 mice as well as the underlying mechanism.
Background/aims
Alzheimer's disease (AD) is the most common neurodegenerative disease, and all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. In this study, we hypothesized that glutamine (Gln) offers protection against oxidative stress injury in SAMP8 mice as well as the underlying mechanism.
Conclusion
This study suggests that glutamine could protect against oxidative stress-induced injury in AD mice via the Wnt3a/β-catenin signaling pathway.
Methods
The SAMP8 mice received glutamine intragastrically for 8 consecutive weeks to evaluate the protective effect of glutamine on oxidative stress in AD mice involving Wnt3a/β-catenin signaling pathway. In addition, rat pheochromocytoma tumor cell line PC12 was pretreated with 32 μM glutamine for 2 h followed by 24 h incubation with 40 μM Aβ25-35 to obtain in vitro data.
Results
In vivo the administration of glutamine was found to ameliorate behavioral deficits and neuron damage, increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP) activity, reduce the malondialdehyde (MDA) content, and activate the Wnt3a/β-catenin signaling pathway in SAMP8 mice. In vitro glutamine treatment decreased the toxicity of Aβ25-35 on PC12 cells and prevented apoptosis. Additionally, glutamine treatment increased SOD and GSH-XP activity and decreased MDA content and increased Wnt3a and β-catenin protein levels. Interestingly, the DKK-1 (Wnt3a/β-catenin pathway inhibitor) decreased the antioxidant capacity of glutamine in Aβ25-35-treated PC12 cells.