Fatty Acids Content And Metabolism Changes In APP/PS1 Double Transgenic AD Mice

BackgroundAlzheimer’s diseases(AD)is the most common form of senile dementia,however the etiology of the disease needs to be detailed more precisely to predict its occurrence and progress,which makes it difficult to prevent and cure.In recent years,data from epidemiological and experimental studies suggest that fatty acids associated with AD: the composition and content of dietary fatty acids can influence the risk of AD,and fatty acid alterations have been found in AD patients compared with normal population.Mitochondria and peroxisomes are involved in β-oxidation of fatty acids.Researches have shown that dysfunction of fatty acid β-oxidation can change the levels of fatty acids in the body,so whether the alterations of fatty acids in AD associated with the dysfunction of fatty acid β-oxidation need to be discussed.ObjectiveIn this experiment,we will compare the composition and content of fatty acids in cerebral cortex,and the levels of mitochondrial and peroxisomal fatty acid β-oxidation related enzymes and factors in the liver between APP/PS1 double transgenic mice and its wild mice,to provide experimental evidence for the relationship between the occurrence of AD and fatty acid content and metabolic function.MethodsPartⅠ: The changes of fatty acids in cerebral cortex of APP/PS1 double transgenic AD miceAPP/PS1 double transgenic AD mice(transgenic group,n=10)and wild mice(wild group,n=10)were used in this experiment.Morris water maze was used to test spatiallearning and memory ability.Gas chromatography was used to analyze the composition and content of fatty acids in cerebral cortex,and biochemical reagent kits were used to measure the levels of serum total cholesterol(TC),triglyceride(TG)and free fatty acids(FFA).PartⅡ: The changes of liver fatty acid β-oxidation related enzymes and factors of APP/PS1 double transgenic AD miceqRT-PCR was used to measure mRNA levels of mitochondrial β-oxidation key enzyme Carnitine palmitoyltransferaseⅠ(CPT1),peroxisomal β-oxidation related enzymes acyl-CoA oxidase(ACOX1),D-bifunctional protein(DBP)and L-bifunctional protein(DBP)and peroxisome proliferator-activated receptorα(PPARα)in the liver,and Western Blot was used to measure protein levels of CPT1,ACOX1 and PPARα.ResultsPartⅠ: Compared with the wild mice,the 4th day escape latency was significantly increased in the transgenic mice(P<0.05),indicating cognitive decline of AD mice;there was no difference in fatty acid types between transgenic mice and wild mice in cerebral cortex,however compared with wild mice,the levels of PUFA(C20:2,C20:4,C22:6)(P<0.05 or P<0.01)and SFA(C15:0)(P<0.05)decreased significantly,the level of MUFA(C24:1)was significantly increased(P<0.05)in the cerebral cortex of transgenic mice.There was no significant difference of serum TC,TG and FFA between transgenic mice and wild mice.(P>0.05)PartⅡ: There was no significant difference of fatty acid β-oxidation related enzymes and PPARα between transgenic mice and wild mice(P>0.05).ConclusionIn APP/PS1 double transgenic mice,there is a significant decrease in the fatty acid levels of C20:2,C20:4,C22:6 and C15:0,and a significant increase in C24:1 level,however there is no significant change of fatty acid β-oxidation related enzymes andfactors,indicating that the dysfunction of fatty acid β-oxidation may not be involved in the alterations of fatty acid content in AD brain.