The Age-related Expression Of Mitochondria Fission And Fusion Protein In The Hippocampus And Frontal Lobe Of Senescence-accelerated Mice

Alzheimer’s disease (AD) is a kind of central nervous systemneurodegenerative disease. It is characterized by the progressive decline ofmemory and cognition, as well as changes in behavior and personality. Thepathological hallmarks of AD are senile plaques and neurofibrillary tangles,accompanied with neuron loss and gliosis. However, the etiology andpathogenesis of AD remains unclear until now. It may involved in the depositof amyloid-β, hyperphosphorylation of tau protein, inflammatory reaction ofgliocyte, polymorphism of apoE gene and mitochondrial dysfunction and soon. Along with the aging of social population, AD patients are becoming moreand more, which has become the fourth cause of death immediately aftercardiovascular disease, cancers and stroke.Given the pathogenesis of AD is very complicated, people made avarious of animal models for AD, but none of them can reproduce and mimicthe main pathology, biochemistry, neurotransmitter and behavior featuresexactly. Among those the senescence-accelerated mouse-prone8(SAMP8) isan ideal animal model for AD relatively, for this kind of mouse not only hasthe deficits of learning and memory, but also exerts the deposit of amyloid-β,senile plaques and immune function disorders. The normally agingsenescence-accelerated mouse-resistant1(SAMR1) strains often be used as thecontrol group for SAMP8mice.Increasing evidence indicate that AD is associated with disorders ofmitochondria fission and mitochondria fusion. mitochondria are dynamicorganelles that continuously change in number and morphology within a cell.In fact, this highly dynamic balance of mitochondrial fission and fusion notonly controls mitochondrial morphology, length, size, and number, but alsoregulates mitochondrial function and distribution. Thus, alterations in mitochondrial fission and fusion can significantly impact neuronal function. Inmammals, mitochondrial fission is mainly controlled by two proteins:dynamin-like protein1(DLP1) and mitochondrial fission1(Fis1). On the otherhand, mitochondrial fusion is regulated by three large GTPases: Mitofusin1(Mfn1), Mitofusin2(Mfn2) and optic atrophy protein1(OPA1).Objective： This study is to observe the age-related expression ofmitochondria fission and fusion protein in the hippocampus and frontal lobe ofthe senescence-accelerated mouse-prone8(SAMP8) and its control group thesenescence-accelerated mouse-resistant1(SAMR1) by RT-qPCR and Westernblot. Our destination is to explore how the abnormalities in mitochondrialfission and fusion impact AD and to provide some experiment evidence forthe pathogenesis and new therapeutic target of AD.Methods：Male healthy SAMP8and SAMR1mice, which aged4,8,10and12months, were used in this study. Every age group included6SAMP8mice and6SAMR1mice. RT-qPCR was used to analyze the alterations of theexpression of DLP1, Fis1, Mfn1, Mfn2and OPA1mRNA in micehippocampus and frontal lobe, and Western blot was used to measure theexpression changes of Fis1, Mfn1and Mfn2protein in mice hippocampus.Results：There were expression of DLP1, Fis1, Mfn1, Mfn2and OPA1mRNA in the hippocampus and frontal lobe of all the mice at different ages.Compared with SAMR1mice at the same age, the expression of DLP1andFis1mRNA in the hippocampus of SAMP8mice decreased at4months(P＜0.05), while increased at8and10months, but both were not of significantstatistical importance(P＞0.05), significantly increased at12months(P＜0.05).Similar changes occurred in mice frontal lobe. Compared with SAMR1mice,the expression of Mfn1and Mfn2mRNA in the hippocampus of SAMP8miceelevated at4,10and12months(P＜0.05), and there were not differences at8months(P＞0.05).Changes of the frontal lobe were likely to that of thehippocampus. Compared with SAMR1mice, the expression of OPA1mRNAin SAMP8mice didn’t change significantly both in hippocampus and frontallobe at all age groups(P＞0.05). The protein expression changes of Fis1, Mfn1 and Mfn2were all similar to that of their mRNA in the hippocampus of allmice.Conclusions：The results of our study indicated that with the ageincreased, there were age-related expression changes of mitochondria fissionand fusion protein in the hippocampus and frontal lobe of SAMP8mice. Theexpression of DLP1and Fis1increased, and the expression of Mfn1and Mfn2also elevated, while that of OPA1didn’t change significantly, which indicatedthat accompanied with aging, the dynamic balance of mitochondrial fissionand fusion was disturbed and mitochondrial fission and fusion was associatedwith the pathogenesis of AD.