The Effect Of Different Intensity Of Treadmill Exercise On The Cognitive Function Of APP/PS1 Mice And The Research On The Mechanism Of Lipid Metabolism

Objective: Alzheimer’s disease(AD)is one of the most common dementia diseases.The main clinical manifestations are progressive learning and memory loss.The main pathological characteristics is β-amyloid(Aβ)deposited in the brain of AD.At present,there are no effective treatment drugs and methods in clinical practice.Therefore,it is of great medical and social value to find economic and effective prevention and treatment methods.Cerebral metabolic disorder is one of the underlying pathophysiological mechanisms of AD,especially the imbalance of cholesterol metabolism in the brain significantly increases the risk of AD.Static lifestyle is an important risk factor affecting the occurrence and progression of AD.Exercise has a neuroprotective effect and can slow the occurrence and progression of AD.However,there are few studies on the mechanism of exercise in preventing and treating AD,and the lack of research on the relationship between the effect of AD prevention and exercise intensity.In this study,Aβamyloid precursor protein(APP)/ presenilin-1(PS1)double transgenic mice were used,and treadmill exercise with different exercise intensity was given for 5 months.Though observed each group’s changes in learning and memory ability,soluble Aβ content in the hippocampus,and related indexes of lipid metabolism in mice.The therapeutic effects of different intensity treadmill exercise on AD model were studied,and the mechanism of lipid metabolism that slowed the progression of AD model disease was further revealed.Methods: In this study,3-month-old wild-type mice(n = 10)and APP / PS1 transgenic mice(n = 30)were selected and divided into the following 4 groups: wild-type mouse control group(Wt C),and transgenic mouse control group(TC),low intensity exercise group(TE1)of transgenic mice,medium intensity exercise group(TE2)of transgenic mice.The mice in the exercise group were given low-intensity and medium-intensity treadmill exercise for 5 months.After exercise,Morris water maze was used to test the learning and memory behavior of mice in each group.After the behavioral test,fasted for12 hours,the blood was collected from the posterior orbital venous plexus after anesthesia,and the blood lipid was measured by colorimetric method;the brain was decapitated,the hippocampus tissue was stripped,and liquid nitrogen was quickly frozen,stored in a-80 ° C refrigerator,left The hippocampus was tested for soluble Aβ content in the hippocampus by Elisa,and the hippocampus on the right was tested by Western blot for ATP-binding cassette transporter A1(ABCA1),liver X receptor(Liver X receptor,LXR),Retinoic X receptor(RXR),apolipoprotein E(Apo E),LDL Receptor Related Protein 1,LRP1,low density lipid Protein content of low-density lipoprotein(LDLR).Results: 1.The results of the Morris water maze showed that treadmill exercise significantly slowed the learning and memory impairment of APP / PS1 transgenic mice,and the difference was significant(P <0.05);the TE2 group was significantly better than the TE1 group,and the difference was significant(P <0.05).2.Compared with the TC group,the total plasma cholesterol(Tch)content in the TE1 and TE2 groups of mice was significantly reduced(P <0.05).but there was not significantly changes between TE1 and TE2 group(P>0.05).Compared with the TC group,the triglyceride(TG)in the plasma of TE1 and TE2 groups showed a downward trend,but the difference was not significant(P> 0.05);TE1 group compared with TE2 group,the difference was not significant in TG(P> 0.05).Compared with the TC group,the plasma low-density lipoprotein cholesterol(LDL-C)content in the TE1 and TE2 mice was significantly reduced,and the difference was significant(P <0.05),there was no significant difference between the TE1 and TE2groups(P> 0.05).Compared with the TC group,the high-density lipoprotein cholesterol(HDL-C)of the mice in the TE1 and TE2 groups,content was significantly increased,the difference was significant(P <0.05);and the TE2 group was significantly higher than the TE1 group,the difference was significant(P <0.05).3.Compared with the TC group,the soluble Aβ1-40 and Aβ1-42 contents in the hippocampus of the TE1 and TE2 groups were significantly reduced,and the difference was significant(P <0.05).The TE2 group was significantly less than the TE1 group,and the difference was significant(P <0.05).4.Compared with the TC group,the levels of Apo E,LRP1 and LDLR proteins in the hippocampus of the TE1 and TE2 groups were significantly increased,and the difference was significant(P <0.05).The Apo E and LRP1 protein levels in the TE2 group were significantly higher than TE1 group,the difference was significant(P <0.05).5.Compared with the TC group,the RXR α and RXR β protein contents in the hippocampus of the TE1 and TE2 groups were significantly reduced,and the difference was significant(P <0.05).The TE2 group was significantly lower than the TE1 group,and the difference was significant.(P <0.05);Compared with the TC group,the levels of LXR β and ABCA1 protein in the hippocampus of the TE1 and TE2 mice significantly increased,and the difference was significant(P <0.05).The LXR β protein content in the TE2 group was significantly lower than TE1 group,the difference was significant(P<0.05).Conclusion: 1.Medium-intensity treadmill exercise is more conducive to reducing learning and memory impairment in APP / PS1 mice than low-intensity treadmill exercise;2.Medium-intensity treadmill exercise is more conducive to reducing APP / PS1 smaller than small-intensity treadmill exercise Soluble Aβ content in rat hippocampus;3.Disorders in regulating lipid metabolism may be a mechanism by which exercise improves learning and memory impairment in AD transgenic mice.