| Objective: Alzheimer’s disease is a kind of complex central nervous system degenerative disease caused by many factors, and it is positively correlated with age. The decline of learning and memory ability is the main clinical manifestation of AD. Excessive deposition of amyloid beta and hyperphosphorylation of tau protein are typical pathological features of AD.Aβ has a strong neurotoxicity, it can not only cause the death of neurons but also activate glial cells release of inflammatory factors. The inflammatory response can also promote the production of more Aβ. At present, the pathogenesis of AD is not clear, there is no hypothesis can fully explain the occurrence and development of AD, and effective drugs and means to treatment AD have not yet appeared. Aerobic exercise is not only a good training methods but also play an important role in the development of brain. More and more studies have confirmed that aerobic exercise can enhance brain function,promote the regeneration of neurons, inhibit the apoptosis of nerve cells and increase the ability of learning and memory. Aerobic exercise can reduce theproduction of Aβ and the release of inflammatory factors, but the study of aerobic exercise and AD is still in the early stage, and the specific mechanism is not clear. Therefore, this study will start from the two aspects of behavior and molecular biology,observing the effect of aerobic exercise on learning and memory ability of AD rats, and through the determination of peripheral inflammatory factors and related signaling pathway of MAPK signal protein to observe whether aerobic exercise can improve the body’s anti-inflammatory ability. The aim is to provide a more solid theoretical basis for the aerobic exercise as a means of preventing and treating AD, and to provide a new thinking to delay the onset of AD, reduce the pain of AD patients and the incidence of AD.Methods: Male SD rats, two months,weight 200±20g, Randomly divided into control group, exercise group, dementia group(Aβ1-42) and dementia exercise group(Aβ1-42/Running). All of the four groups of rats were buried tube operation, and the control group and the dementia group did not carry out any running training. Exercise group and dementia exercise group for a period of aerobic exercise, five days a week, rest for two days, a slope of zero degrees.Rats at first weeks and second weeks to 10m/min at the speed of running two15 min, the middle of the rest 5min. Third weeks to 15m/min the speed of running three 15 min, every 15 min rest 5min. Fourth weeks to 15m/min the speed of running four 15 min, every 15 min rest 5min. After two weeks ofaerobic training, the dementia group and the dementia group were injected with Aβ1-42. Then through Morris water maze test to test the spatial learning and memory ability of rats in each group. The technology of molecular biology analysis: ①Test in peripheral blood of inflammatory factor of tumor necrosis factor alpha and interleukin 1 beta expression changes by ELISA. ②Detection of inflammatory signaling pathway specific c-Jun N-terminal kinase of c-Jun N-terminal kinase(JNK), P38 mitogen mitogen activated protein kinase( P38MAPK) and ERK extracellular regulated protein kinase(ERK) changes by western blot. Data were expressed as mean±standard error(Mean±SEM). Using Sigmaplot11.0 software for statistical analysis of the data,Using mapping.P<0.05 indicates that there is a significant difference, P<0.01 indicates that there is a very significant difference.Result:1. ① Morris water maze navigation experiment results show that with the increasing number of days of swimming rats, each group of rats to find the incubation period and the total distance of the swimming pool is also significantly reduced. From swimming training in rats of 1-5 days, through the establishment of a beta AD model group rats and the control group compared to finding underwater hidden platform latency and swimming distance were increased significantly(P<0.01), indicating that decreased the ability of learning and memory of the ad model rats. Compared with the AD model group and theexercise treatment group, the escape latency was significantly lower than that of the AD model group(P<0.05) in the first 1~5 days. On the first 1~4 days, the total swimming distance in the exercise group was significantly lower than that in the AD model group(P<0.05). It indicates that aerobic exercise can improve the impairment of learning and memory function induced by A, and has a protective effect. ② The hidden platform removal, to carry out space exploration experiment, the results found that AD model group in the original hidden platform quadrant swimming time and the total swimming time and the percentage of the control group compared to the significantly decreased(P<0.01). And compared with AD model rats in the original hidden platform quadrant swimming distance and the total distance and the percentage of the control group also significantly decreased(P<0.01), indicating a beta group rats showed significant impairment of spatial memory. And simply have the exercise group and compared to the control regardless of the percentage of time or distance percentage, the percentage activity in the original platform quadrant did not appear significant difference(P>0.05), indicating that the pure oxygen exercise does not directly enhance hippocampal dependent spatial reference memory consolidation. In the exercise group, the percentage of both time and distance was significantly increased compared with the AD model group(P<0.01). This result indicates that A can induce the loss of spatial reference memory in rats, and aerobic exercise can improve the damage. ③This result indicates that Aβ can induce the loss of spatial learning and memory, andaerobic exercise can improve the damage. To display visible platform test, There was no statistical difference in the time of the platform and swimming speed of the rats in each group(P>0.05). The effect of visual acuity and motor ability of the rats on the preliminary experimental results were excluded.2. Enzyme linked immunosorbent assay results showed that by rats were detected in the peripheral blood of TNF alpha and IL-1 beta expression content found that pure with aerobic exercise group and blank control group, TNF alpha and IL-1 beta both inflammatory factor does not appear significant difference(TNF-α,P=0.746; IL-1β,P=0.883). The results illustrate simple aerobic exercise and not in peripheral blood of inflammatory cytokines caused any effect.Compared with the control group, the contents of TNF-α and IL-1β in peripheral blood were significantly increased in AD model group(P<0.01). The content of the two kinds of inflammatory factors in the exercise therapy group were significantly lower than those in the AD model group(P<0.05). The results said that Abeta affects the immune function of the body which leads to the peripheral inflammatory cytokines in peripheral blood expression was increased,and aerobic exercise can relieve amyloid beta induced peripheral blood inflammatory factors expression upregulation.3. MAPK signaling pathway related proteins were determined by Westernblot:ERK protein, P38 MAPK protein and JNK protein. ①In the dementia group the phosphorylation level of ERK protein compared with other three groups were significantly reduced, especially the ratio of phosphorylated ERK and totalprotein decreased significantly(P<0.01). It showed that ERK significantly inhibited the activity of Aβ. However, the phosphorylation level of ERK protein in the dementia exercise group was significantly increased compared with dementia group(P<0.05). Through the comparison of the total ERK protein and beta actin we found in all the groups of total protein levels and no significant change(P>0.05) that a beta and aerobic exercise is through ERK phosphorylation of the viability of cells to control did not affect the expression of total ERK protein. ②In the determination of P38, it was found that the ratio of P38 to total protein decreased significantly in dementia group(P<0.05), while dementia exercise group reversed this trend, and the level of phosphorylated P38 was significantly increased(P<0.01). Aβ makes the brain damage factor P38 over activated, and aerobic exercise can change this effect, playing a important role in neural protection. Compared with other groups.Through the comparison of the p38 protein and beta actin we found in all the groups of total protein levels and no significant change(P>0.05) that have a beta and aerobic exercise are through the phosphorylation of p38 of on cell activity regulation did not affect the expression of p38 protein. ③ the phosphorylation level of JNK in dementia group was significantly higher(P<0.01), and the ratio of phosphorylated JNK to total protein was significantly higher(P<0.05).Dementia exercise group compared with dementia group decreased the phosphorylation of JNK levels(P<0.01). This shows that Aβ can cause brain damage factor JNK of the excessive phosphorylation, and aerobic exercise canreduce the reaction.Through the comparison of the total JNK protein and beta actin we found in all the groups of total protein levels and no significant change(P>0.05) that a beta and aerobic exercise is through the phosphorylation of JNK of on cell activity regulation did not affect the total JNK protein expression.Conclusion: Aβ can significantly damage the spatial learning and memory abilities of rats, and the aerobic exercise can improve the damage. Aβ can cause the increase of the two kinds of inflammatory factors, TNF- alpha and IL-1 beta,which affect the body’s immune system. Aerobic exercise can reduce the peripheral inflammatory response induced by Aβ. At the same time the excessive activation of Aβ induced MAPK signaling pathway related proteins,resulting in damage to neurons and cognitive function obstacle. Aerobic exercise to prevent inflammation caused by Aβ by changing the expression of ERK/P38/JNK. Aerobic exercise can play a neuroprotective role through regulating neural immune function, improving the ability of learning and memory. |
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