Amyloid-β (25–35) regulates neuronal damage and memory loss via SIRT1/Nrf2 in the cortex of mice

Abstract

Alzheimer’s disease (AD) is the most common type of dementia. AD is pathologically characterized by synaptic dysfunction and cognitive decline due to the aggregation of a large amount of amyloid-β (Aβ) protein in the brain. However, recent studies have discovered that the Aβ is produced as an antimicrobial peptide that acts against bacteria and viruses. This has renewed interest in the effect of Aβ on AD. Thus, in this study, we investigated the different concentrations of Aβ25–35 on neuroprotection and further explore the related mechanisms. Firstly, we detected the cognitive function using the Y-maze test, novel object recognition memory task and Morris water maze test. Then, we analyzed the ultrastructure of synapses and mitochondria, in addition to evaluating SOD levels. We also examined the effect of Aβ25–35 on the viability and structure of the primary neurons. The western blot analysis was used to measure the protein levels. The results showed that mice treated with high concentration of Aβ25–35 impaired the learning-memory ability and disordered the structure of neurons and mitochondria. Meanwhile, high concentration of Aβ25–35 decreased the SIRT1/Nrf2 related antioxidant capacity and induced apoptosis. In contrast, mice treated with low concentration of Aβ25–35 increased SOD levels and SIRT1/Nrf2 expressions, and induced autophagy. Our data suggest that low concentration of Aβ25–35 may increase SOD levels through SIRT1/Nrf2 and induce autophagy.