| Alzheimer’s disease(AD)is a neurodegenerative disease characterized by a decline in cognitive learning ability.The onset period is hidden and the treatment cost is high,which brings a heavy burden to the family and society.Exercise increases cerebral blood volume,reduces reactive oxygen species and oxidative stress,reduces A β load and tau hyperphosphorylation,modulates brain-derived neurotrophic factor,modulates synaptic plasticity,improves neurogenesis,and increases pro-angiogenic growth factors It can effectively improve cognitive function and reduce the incidence of neuropsychiatric diseases in AD patients.However,different exercise cycles and exercise loads will produce different benefits for AD patients,and the molecular mechanism by which exercise improves AD symptoms is still unclear.Based on this,this study analyzed the effects of different loads of aerobic exercise on cognitive function in APP/PS1 transgenic AD mice,and explored its molecular mechanism.Objective:Taking APP/PS1 transgenic AD mice as experimental objects,the effects of aerobic exercise for 4 weeks,6 weeks and 8 weeks on the learning and memory ability of APP/PS1 transgenic AD mice were investigated.At the same time,the hippocampus of mice plays an important role in cognitive function.As a starting point,we analyzed the expression and trend of aerobic exercise on Metrnl factor and GFAP glial fibrillary acidic protein,which are highly related to cognitive function,in the hippocampus of mice,in order to explain that aerobic exercise can improve APP/PS1 transgenic AD.Possible molecular mechanisms of murine cognitive function.Methods:A total of 52 APP/PS1 transgenic AD mice and normal C57 mice were selected and randomly divided into non-transgenic quiet group(Non-Transgenic type Sed,NT-Sed)and non-transgenic exercise group(Non-Transgenic type exercise,NT-Exe).)12 mice in each group,transgenic quiet group(Transgenic type Sed,TG-Sed),transgenic exercise group(Transgenic type exercise,TG-Exe)(in view of the poor resistance and relatively high mortality of transgenic mice,in order to prevent experimental Accidental death occurred during the process,and the transgenic exercise and quiet groups both increased by 2 mice),with 14 mice in each group.Firstly,the gene identification of hybrid offspring mice was carried out,and double transgenic mice and normal mice were isolated.Secondly,the mice in the NT-Sed group and the TG-Sed group were kept in separate cages and kept quietly without any intervention.The mice in the NT-Exe group and the TG-Exe group underwent treadmill training for 4 weeks,6 weeks,and 8 Wednesdays.After each exercise cycle,the learning and memory ability of the mice was tested by the water maze test.24 hours after the end of the behavioral experiment,the mice were anesthetized and decapitated,and the hippocampus tissues of the mice were taken and placed in a-80℃ ultra-low temperature refrigerator for testing.Finally,q-PCR was performed to detect the transcription levels of Metrnl factor and GFAP glial fibrillary acidic protein,which are highly correlated with cognitive function in the hippocampus of mouse brain.Results:(1)The gel imaging after agarose gel electrophoresis showed that 500bp-1000bp appeared as the PS1 gene band.In the corresponding 17 lanes,the APP/PS1 mice corresponded to the 500bp-1000bp bright band region.Confirmed that 12 of the 17 mice were APP/PS1 transgenic AD mice(2)After the water maze behavioral test,compared with the NT-Sed group,the escape latency of the TG-Sed group was significantly increased,and the number of crossing the platform and the percentage of the platform quadrant were significantly reduced.Compared with the mice in each non-exercise group,after 4 weeks,6 weeks and 8 weeks,treadmill exercise can significantly down-regulate the escape latency,significantly up-regulate the number of crossing the platform,and the distance of the platform quadrant in the TG-Exe group and NT-Exe mice.percentage.Comparing the effects of three different exercise cycles on the learning and cognitive ability of mice,it was found that the longer the exercise cycle,the better the effect of improving cognitive ability,and the most significant effect after eight weeks of exercise.(3)After detecting the transcription levels of Metrnl factor and GFAP glial fibrillary acidic protein,compared with NT-Sed group mice,the expression of Metrnl factor in TG-Sed group mice was significantly decreased,and GFAP glial fibrillary acidic protein The expression level increased strongly,and exercise effectively inhibited the strong expression of GFAP glial fibrillary acidic protein in mice in TG-Exe group.After 4 weeks,6 weeks and 8 weeks,treadmill exercise can significantly increase the expression of Metrnl factor,and gradually increase the expression of GFAP glial fibrillary acidic protein in TG-Exe group and NT-Exe mice.The expression levels of the two were affected,and it was found that the overall trend was increasing,and the expression level was the highest after eight weeks of exercise.Conclusions:(1)APP/PS1 mice showed cognitive impairment,and their learning and memory abilities were lower than those of normal C57 mice.Aerobic exercise enhanced the learning and memory ability of APP/PS1 mice and normal C57 mice,and effectively improved the cognitive function level of APP/PS1 mice and normal C57 mice.(2)Different stages of aerobic exercise have different levels of cognitive improvement in APP/PS1 mice and normal C57 mice.With the extension of the aerobic exercise cycle,the overall increase trend,and the cognitive ability of mice is improved.(3)Aerobic exercise increased the expression levels of Metrnl factor and GFAP glial fibrillary acidic protein in the hippocampus of APP/PS1 transgenic AD mice,and the cognitive function of AD mice was improved at the same time.Therefore,the regulation of Metrnl factor and GFAP glial fibrillary acidic protein by exercise may be one of the molecular mechanisms that exercise improves cognitive function in AD mice. |
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