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

Lili Feng; Bowen Li; Mengxin Cai; Zezhou Zhang; Yifang Zhao; Su Sean Yong; Zhenjun Tian

doi:10.1016/j.expneurol.2023.114559

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

Exp Neurol. 2023 Dec:370:114559. doi: 10.1016/j.expneurol.2023.114559. Epub 2023 Oct 1.

Authors

Lili Feng¹, Bowen Li², Mengxin Cai³, Zezhou Zhang³, Yifang Zhao³, Su Sean Yong⁴, Zhenjun Tian⁵

Affiliations

¹ Department of Sport and Exercise Science, College of Education, Zhejiang University, Hangzhou 310058, China; Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi'an 710119, China. Electronic address: fenglili@zju.edu.cn.
² Department of Sport and Exercise Science, College of Education, Zhejiang University, Hangzhou 310058, China. Electronic address: libowen@zju.edu.cn.
³ Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi'an 710119, China.
⁴ Department of Sport and Exercise Science, College of Education, Zhejiang University, Hangzhou 310058, China.
⁵ Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi'an 710119, China. Electronic address: tianzhj@snnu.edu.cn.

PMID: 37788754
DOI: 10.1016/j.expneurol.2023.114559

Abstract

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.

Keywords: Inflammation; Myocardial infarction; Oxidative stress; Prefrontal lobe; Resistance exercise; SESN2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism
Animals
Humans
Inflammation
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction* / metabolism
Oxidative Stress
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
Resistance Training*
Sestrins / metabolism
Signal Transduction

Substances

AMP-Activated Protein Kinases
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
SESN2 protein, human
Sestrins