| ObjectiveDiffusion tensor imaging(DTI)and magnetic resonance spectroscopy(MRS)techniques were used to detect the changes in hippocampal white matter and neurometabolism of high-fat diet ApoE-/-mice,to explore the effect of swimming exercise and diet control on the cognitive function of ApoE-/-mice fed high-fat diet and its correlation with the two pathways of SIRT1-PGC1-1α-BDNF and SIRT1-NF-κBp65,explore the mechanism of swimming exercise and diet control to improve cognitive function,and provide scientific prevention and treatment measures for cognitive dysfunction caused by high-fat diet.Method20-week-old ApoE-/-mice were randomly divided into five groups: control group(C group),high-fat diet group(HF group),diet control group(D group),swimming group(E group),and diet control +Swimming group(DE group),each group contains 12 animals.The mice in the HF,D,E,and DE groups were fed high-fat diet(21% fat,0.15%cholesterol)for 8 weeks.The control group had a normal diet and was given sufficient drinking water.After 8 weeks of high-fat feed,the D,E,and DE groups switched to normal feed after the high-fat feed.The C and HF groups maintained their original diets.At the same time,the E and DE groups were fed without weight-bearing Swimming.Weigh the weight of the mice every week.The new object recognition experiment examines the space exploration ability and learning and memory ability of ApoE-/-mice;Diffusion tensor imaging(DTI)detects hippocampal white matter and calculates FA value;Magnetic resonance spectroscopy(MRS)detects hippocampal neurometabolic compound choline complex Changes in the content of serotonin(Choline,Cho),N-acetylaspatate(NAA),and Myo-Inositol(MI);Western blot detection of hippocampal SIRT1,PGC-1α,BDNF and NF-κBp65,IL-1β,TNF-α protein expression;immunohistochemical method to observe glial fibrillary acidic protein(GFAP)in hippocampus CA1 area,calcium ion adaptor protein-1(Ionized calcium bindingadaptor molecule-1,Iba-1).Result(1)Weight: Compared with the control group,the weight of the high-fat diet group increased significantly(P<0.01);after intervention,compared with the high-fat diet group,the weight of the diet control group,swimming group,diet control + swimming group decreased significantly(P<0.01);Compared with the diet control group and the swimming group,the diet control + swimming group lost significantly(P<0.05).(2)Behavior: The results of the object recognition test showed that compared with the control group,the high-fat diet group had a significant decrease in the 1-hour and 24-hour discrimination index of new objects in the high-fat diet group(P<0.01);compared with the high-fat diet group,The 1-hour and 24-hour discrimination index of the diet control group,swimming group,and diet control + swimming group increased significantly(P<0.01);compared with the diet control group,the 1-hour and 24-hour discrimination index of the diet control + swimming group increased(P<0.01)).The Y maze results showed that compared with the control group,the high-fat diet group spontaneous alternate reaction rate was significantly lower(P<0.01);compared with the high-fat diet group,the diet control group,swimming group,diet control + swimming group spontaneous alternate reaction The rate increased significantly,and the difference was statistically significant(P<0.01);compared with the diet control group,the spontaneous alternate reaction rate of the diet control + swimming group increased(P<0.01).(3)DTI: FA values ??of bilateral hippocampus in different groups of ApoE-/-mice showed that in the left hippocampus of mice,compared with the control group,the FA value of the high-fat diet group was significantly decreased(P<0.01);Compared with the high-fat diet group,the FA value of the diet control group,swimming group,and diet control + swimming group all increased(P<0.01),and the FA value of the diet control +swimming group was significantly higher than that of the diet control group(P< 0.01).In the right hippocampus of mice,the FA value of the high-fat diet group was significantly lower than that of the control group(P<0.01);compared with the high-fat diet group,the FA value of the diet control group,swimming group,diet control + swimming group All were increased(P<0.05,P<0.05,P<0.01),and the FA value of the diet control +swimming group was significantly higher than that of the diet control group,and the difference was not statistically significant.(4)MRS: In the left hippocampus,compared with the control group,the content of NAA/Cr and Cho/Cr in the high-fat model group decreased(P<0.01),and the content of MI/Cr increased significantly(P<0.01);Compared with the diet group,the NAA/Cr and Cho/Cr contents of the diet control group,the swimming group and the diet control +swimming group increased(P<0.01),and the MI/Cr content was significantly reduced(P<0.01).The diet control + swimming group was smaller The content of NAA/Cr and Cho/Cr in mice was higher than that of the diet control group,and the difference was statistically significant(P<0.01);the MI/Cr content of the diet control + swimming group was lower than that of the diet control group,and the difference was statistically significant(P<0.01).In the right hippocampus,compared with the control group,the content of NAA/Cr and Cho/Cr in the high-fat model group decreased(P<0.01,P<0.05),and the content of MI/Cr increased significantly(P<0.01);compared with the high-fat diet Compared with the group,the NAA/Cr and Cho/Cr content of the diet control group,the swimming group and the diet control + swimming group increased(P<0.01),and the MI/Cr content significantly decreased(P<0.01);the diet control + swimming group mice The content of NAA/Cr and Cho/Cr in the diet control group was higher than that of the diet control group,and the difference was statistically significant(P<0.05,P<0.01).The MI/Cr content of the diet control + swimming group was lower than that of the diet control group,and there was no difference Statistical significance.(5)Protein expression of SIRT1,PGC-1α,BDNF,NF-κBp65,IL-1β,and TNF-α in the hippocampus: Compared with the control group,the high-fat diet group SIRT1,PGC-1α,BDNF protein expression decreased(P<0.01,P<0.05,P<0.01),the expression of NF-κBp65,IL-1β,and TNF-α increased(P<0.05,P<0.01,P<0.05);compared with the high-fat diet group,the diet control group,The expression of SIRT1 increased in the swimming group and the diet control + swimming group(P<0.01),the expression of PGC-1α increased(P<0.05,P<0.01,P<0.01),the expression of BDNF increased(P<0.01),and NF-κBp65 Protein expression decreased(P<0.05,P<0.01,P<0.01),IL-1β protein expression decreased(P<0.01,P<0.05,P<0.05),TNF-α protein expression decreased(P<0.05);and Compared with the diet control group,the SIRT1 protein expression in the diet control + swimming group increased(P<0.01),the expression of PGC-1α increased(the difference was not statistically significant),the expression of BDNF increased(P<0.01),and the expression of NF-κBp65 protein Decrease(P<0.05),the expression of IL-1β and TNF-α decreased,and the difference was not statistically significant.(6)The expression of GFAP and IBA1 in the CA1 area of ??the mouse hippocampus: Compared with the control group,the expression of GFAP and IBA1 increased in the high-fat diet group;compared with the high-fat diet group,the diet control group,the swimming group and the diet control + swimming group GFAP,IBA1 expression decreased.DiscussionHigh-fat diet can cause neuroinflammation and promote cognitive decline.It is closely related to the SIRT1-NF-B inflammatory pathway,and regulates hippocampal neurometabolism and white matter fiber abnormal connection by affecting the PGC1-1α-BDNF pathway;swimming and diet Control can improve neuroinflammation and cognitive decline induced by high-fat diet,which is closely related to the SIRT1-NF-B/PGC1-1α pathway. |
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