Resistance exercise alleviates the prefrontal lobe injury and dysfunction by activating SESN2/AMPK/PGC-1α signaling pathway and inhibiting oxidative stress and inflammation in mice with myocardial infarction.

OBJECTIVES: Myocardial infarction (MI) induces inflammatory response and oxidative stress in the brain, which would be one of the causes of cardiac dysfunction. Exercise training is viewed as a feasible strategy to improve cardiac function of the infarcted heart. The aim of this study was to investigate whether exercise training could alleviate MI-induced prefrontal lobe injury via activating Sestrin2 (SESN2) signaling and inhibiting oxidative stress and inflammation. METHODS: Male C57BL/6 mice were divided into five groups: control group (CON), aerobic exercise group (AE), resistance exercise group (RE), whole-body vibration group (WBV) and electrical stimulation group (ES); and three groups: sham-operated group (S), sedentary MI group (MI) and MI with resistance exercise group (MRE). After four weeks of training, sensorimotor function, spatial learning, long-term and spatial memory, and cardiac function were detected. Then, mice were euthanized, and the prefrontal areas were separated for HE, Nissl, SESN2, microtubule-associated protein 2 (MAP2), neuron-specific nucleoprotein (NeuN), and TUNEL staining. Activation of SESN2/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) signaling pathway and expression of proteins related to oxidative stress, inflammation and apoptosis in the prefrontal lobe were detected by western blotting. RESULTS: Different types of exercise training all activated the SESN2/AMPK/PGC-1α signaling pathway, and the effect of RE is the best. RE improved sensorimotor, learning, and memory impairments, increased the expressions of antioxidant, anti-inflammatory and anti-apoptotic proteins, reduced oxidative stress, inflammation and apoptosis, ultimately alleviated the prefrontal lobe injury and dysfunction in mice with MI. CONCLUSION: RE alleviates MI-indued prefrontal lobe injury and dysfunction by inhibiting the levels of oxidative stress, inflammation and apoptosis, partially via activating SESN2/AMPK/PGC-1α signaling pathway.