The age-dependent impacts of treadmill exercise on cognitive impairments by reducing inflammation and oxidative stress in the hippocampus of morphine-exposed rats: the role of SIRTs 3 &4 and BDNF.

Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying on the role of oxidative and inflammatory factors as well as SIRT 3, SIRT 4, and BDNF. 56 male Wistar rats were allotted in 8 groups, 4 for young and 4 for old rats.The groups include 1. Control; 2. Exercise; 3. Morphine exposed; 4. Morphine exposed + Exercise.The rats in morphine-exposed groups received morphine for 21 days, and the rats performed treadmill exercises for 4 weeks. The behavioral tests included Morris water maze (MWM), Open field test (OFT), Elevated plus maze (EPM), and Novel object recognition test (NOR), which were done to evaluate cognitive function. The gene expression of TNF, IL-6, BDNF, SIRT 3, and SIRT 4 was measured in the hippocampus tissue by RT-PCR. Also, the levels of MDA, TAC, SOD and GPX were assessed using by related kits. Our results showed that morphine exposure in both young and old rats resulted in cognitive impairments and increased anxiety-like behaviors. Also, morphine exposure reduced BDNF, SIRT1, and SIRT4 and increased TNF and IL-6 gene expression in the hippocampus of rats. However, exercise could improve cognitive impairments and anxiety in both young and old rats and reduce TNF, IL-6, and MDA and elevation of BDNF, SIRT 3, and SIRT 4 gene expression and TAC, SOD, and GPX levels in the hippocampus tissue. Exercise could improve cognitive impairments following morphine exposure in young and old rats by reducing inflammation and oxidative stress and increasing expression of BDNF, SIRT 3, and SIRT 4.