Beneficial effects of resistance exercise in improving cognitive functions and reducing neuropathology in postoperative cognitive dysfunctions and Alzheimer’s transgenic mice

Abstract

Exercise is well-known to have great beneficial effects to the whole body. While majority of research demonstrates neuroprotective effects of aerobic exercise, a certain large population of patients who are too old or suffer from motor problem cannot gain the benefits of aerobic exercise. Some Alzheimer’s disease (AD) patients cannot even perform proper aerobic exercise. Therefore, investigating the effects of resistance exercise is important for patients lying on the bed and for some AD patients. We hypothesize that resistance exercise can improve cognitive functions. We proved the correction of cognitive functions by two experimental models. One model was the risk factor for developing dementia, namely postoperative cognitive dysfunctions (POCD), using C57BL/6 mice. Another model was to use AD transgenic mice bearing three types of mutations (3xTg mice). Resistance training was accomplished by a ladder-climbing protocol for 5 weeks with 3-4 training sessions per week. For each session, mice were forced to climb up a 1-meter ladder with progressively larger weight attached to tail for 15 times with 2 minutes rest during each trail. Effects of resistance training on cognition and muscle strength were checked by Y-maze and weight lifting test, respectively. For 3xTg mice, we used 9-month-old mice. For POCD, laparotomy was performed using aseptic procedures under sevoflurane (3-4%) as anesthesia (~20 min). Cognitive functions were assessed by Y-maze test and novel object recognition (NOR) test 2 weeks afterwards. Levels of synaptic proteins in the hippocampus were detected by western blot. Cytokines levels were measured by their expression of mRNA and proteins. Our results showed that resistance exercise could revert the cognitive dysfunctions induced by laparotomy and attenuate progressive cognitive loss in 3xTg mice in Y-maze test. Furthermore, western-blot analysis showed that it could ameliorate loss of synaptic proteins, tau protein phosphorylation, and inflammatory cytokines. Our studies demonstrate that resistance exercise can be an alternative way of exercise that can provide to patients who have motor deficit or difficulty in working out for aerobic exercise.