The Effect of Aerobic Training and Resveratrol on Ferroptosis in a Rat Model of Alzheimer's Disease

Ferroptosis is a type of iron-dependent cell death that has been identified in the brains of patients with Alzheimer's disease (AD). Exercise and resveratrol (RSV) can delay neurodegenerative diseases, especially AD. The present study aimed to investigate the effect of aerobic training and RSV on hippocampal ferroptosis in a rat model of AD.

In this experimental study, 35 male Wistar rats were divided into 5 groups: Control (CTRL), AD, AD-Training (ADT), AD-RSV (ADRSV), and AD-Training-RSV (ADTRSV). The ADRSV and ADTRSV groups received 20 mg/Kg of RSV orally during the intervention period. An aerobic exercise program including running on a treadmill with a speed of 6-18 meters per minute, was performed 5 days a week for eight weeks. Iron and GSH levels were measured by ELISA and gene expression by Real time-PCR method.

AD induction caused a significant increase in iron level and a decrease in GSH, Gpx4, Nrf2, and HO-1 expression compared to the CTRL group. Exercise and RSV decreased iron and increased GSH, Nrf2, and HO-1 values compared to the AD group. Moreover, a significant increase was observed in the levels of GSH, Gpx4, Nrf2, and HO-1 in the ADTRSV group compared to the ADT and ADRSV groups compared to the other groups.

AD induction was associated with an increase in ferroptosis indices, and aerobic exercise activity and RSV administration improved this process. Considering the effect of aerobic training and RSV, these two treatment methods can be used together to improve neurodegenerative diseases, such as AD.