| Alzheimer's disease (AD), which is characterized by progressive loss of neurons, accumulations of senile plaques and neurofibrillary tangles, is the most common cause of dementia. It has been reported that mutations in presenilin genes are associated with the early onset of Familial Alzheimer's disease (FAD). Presenilin1(PS1) and presenilin2(PS2), two homologous genes that shared～67% amino acids, are considered to be the active sites of y-secretase complex which is responsible for the proteolytic processing of amyloid precursor protein (APP). Forebrain-specific conditional PS1 and PS2 double knockout mice (DKO mice) indeed appeared decreased Aβcontent, but also exhibited several of the Alzheimer-like neurodegenerative symptoms, including impairments in synaptic plasticity and hippocampus-dependent memory, severe shrinkage of the cortex, neuronal atrophy, tau phosphorylation and enlargement of the lateral and third ventricles. However, the exactly molecular mechanism of AD and its risk factors have not been elucidated yet. Furthermore, there is no effective treatment for AD.Exercise is good for health. Exercise can be divided into aerobic exercise and anaerobic exercise according to the source of the energy of muscle contraction from aerobic or anaerobic metabolism. Aerobic means "with oxygen", and refers to the use of oxygen in the body's metabolic or energy-generating process. Resistance training is a form of strength training in which each effort is performed against a specific opposing force generated by resistance. Strength training is the use of resistance to muscular contraction to build the strength, anaerobic endurance and size of skeletal muscles. Strength training is primarily an anaerobic activity. Exercise may improve neurodegenerative symptoms of AD patients and may delay their developments of neurodegenerative symptoms. It is still controversial whether aerobic training can improve neurodegenerative symptoms of AD model mice. Furthermore, it is rarely reported that resistance training effect on the cognitive ability of the AD model mice. Therefore, we want to observe the cognitive changes of DKO mice using aerobic training and resistance training. Generally speaking, aerobic training and resistance training were administrated on 6-month-old DKO mice for 10 weeks respectively. Behavioral tests were applied to test the cognitive abilities. Inflammatory responses were detected and primary mechanisms were explored.1. Effect of exercises on behavioral tests of DKO mice6-month-old DKO mice were respectively given aerobic training and resistance training for 10 weeks, then open-field test, novel object recognition task and fear conditioning were applied to test the abilities of locomotion as well as learning and memory. After 10 weeks' aerobic training and resistance training, the results of open-field test showed that aerobic training and resistance training had no significant effect in the locomotion of the DKO mice. The results of novel object recognition task indicated that aerobic training and resistance training had no significant difference in the learning and memory. The results of fear conditioning revealed that resistance training significantly improved the hippocampus-dependent and amygdale-dependent memory.From the results of behavioral tests, we can conclude that resistance training can ameliorate hippocampus-dependent and amygdale-dependent memory and has a significant difference. 2. The possible mechanisms that exercises partially improve the behavioral tests of DKO miceTo investigate the possible mechanisms that exercises partially improve the behavioral tests of DKO mice, Leukocyte number, ELISA, Western blotting were carried out to determine the effect of aerobic training and resistance training on the inflammation response. It is found that Leukocyte number in the group of sedentary DKO was significantly increased than the group of sedentary CON. But there was no significantly difference in three DKO groups. IL-1βlevel in the group of sedentary DKO was significantly higher than in the group of sedentary CON. IL-1βlevel in the groups of CON aerobic training and CON resistance training were significantly lower than that in the group of sedentary CON. However, there was no significant difference in three DKO groups. Western blotting shows that the GFAP levels in groups of DKO aerobic training and DKO resistance training were significantly lower than the group of sedentary DKO silence in the cortex. But there was no significantly difference in the hippocampus. Western blotting shows that the CD68 level was no difference in three CON groups and three DKO groups.From these results, we concluded that resistance training improve learning and memory of DKO mice may not due to its effect on inflammation response. |
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