ApoE4 Induce Depression‐like Behaviors Of Mouse By Regulate Glucose Metabolize Of Brain

[Objective] depression is one of the most common mood disorders, but the etiology and pathological mechanism of it is still unclear. this paper aims at the rate of depression spontaneously and after modeling in the different background in Apo E(Apolipoprotein E, Apo E) mice, and explore the possible mechanism from the whole to the molecular mechanism by the use of vivo imaging and other research methods.[Method] 1, SPF class 3, 8, 18 month old Apo E3 and Apo E4 male mice and same month old wide type mice, randomized divided into 6 group, each group 12 to 16 mice, observe the depressive like behavior by SPT(Sucrose preference test)、TST(Tail suspension test,)、OFT(Open field test); use two methods of depression like behavior of CUMS(chronic unpredictable mild stress) and FST(Force swimming test) at age in 3 、 8 Apo E3, E4 mice to observe the rate of depression, with the same age and genotype were used as control. 2, By the use of PET-CT, use [18F]FDG as tracer to study the change of glucose metabolism before and after depression in different month old Apo E3 and Apo E4 mice; Using [18F]MPPF(18F-fluoro-N-[2-[1-(2-methoxypheyl)- 1-piperazinyl] ethyl-N-2pridinyl-benz amide) as tracer, to study the changes of 5-HT1 A before and after depression model in different month old Apo E3 and Apo E4 mice. 3, Detect ATP(Adenosine triphophate) content in different month old and different genotypes of mice by fluorescence enzyme mark instrument, research the change of Glut1(Glucose transporters 1) 、 Glut3(Glucose transporters 3) 、 Ip3r2(Inositol triphosphate receptor 2), Apo E in the cortex by western blot to detect the possible mechanism of Apo E4 genotype effect depression like behaviors.[Results] 1, FST and CUMS got a similar success rate of modeling method of depression. Sugar consumption, the tail suspension test, open field test had the same sensitivity to detect the depressive behavior. 2, No significant difference between the young Apo E3, Apo E4 mice in the mold of depression depression like behavior. There was a correlation between the Apo E4 genotype and depression, and this association occurs only in old age. 3, Spontaneously decreased glucose metabolism were observed in middle-aged mice. Glucose metabolism decreased more obviously after FST and CUMS, and the Apo E4 is more serious than type Apo E3, this can be observed in 3 month old mice. 4, Efficiency of the automatic [18F]MPPF synthesis method is more purity and specific activity than traditional methods, and 5-HT1 A receptor activity decreased significantly after modeling, more obviously in 8 month old Apo E4 than the Apo E 3 type mice. 5, Apo E4 mice had spontaneous decreased in the content of ATP, after the FST modeling all the genotypes of the mice appeared decreased the content of ATP, and middle age Apo E4 mice reduced more significantly than type Apo E3 in same age. 6, IP3 R, Glut3, Apo E content were not related to the depression like behaviors, the content of Apo E4 always less than Apo E3. 7, The decreased content of Glut1 were observed after FST, and the Apo E4 mice showed more serious than Apo E3 mice in middle age.[Conclusion] 1, The both technique of FST and CUMS had equal efficiency to simulate the depression like behavior in mice, sugar consumption, the tail suspension test, open field test had equal efficiency to detect mouse depression like behavior, Efficiency of the automatic [18F]MPPF synthesis method is more purity and specific activity than traditional methods. 2, Apo E4 reduce the glucose metabolism of glial cells by down-regulation theexpression of Glut1, resulting in a decrease in ATP content, and showed susceptibility to depression, and that susceptibility is age related.