The Role Of Necroptosis In The Zebrafish Model Of Alzheimer’s Disease Induced By Aluminum

Objective:To induct zebrafish model of Alzheimer’s disease by aluminium chloride and to investigate the role of necroptosis in the Zebrafish model of Alzheimer’s disease induced by aluminum.Methods:8 months old adult zebrafish(TU)were randomly divided into 4 groups with 25 fish in each group.The zebrafish was soaked in aluminium chloride solution for 30 days at the concentrations of 0 μg/L,20 μg/L,100 μg/L,and 500 μg/L as control,low-dose,mid-dose,and high dose treatment groups.The PH of aluminium chloride solution of each group was 6.4.The learning and memory abilities of zebrafish was tested by T-MAZE;the brain tissue content of aluminium element was detected by graphite furnace atomic absorption spectrometry;the brain tissue content of APP、Aβ1-42、Aβ1-40 were detected by ELISA;the related genes’ expression of mTOR signaling pathway,Alzheimer’s disease and Necroptosis were measured by Real Time PCR.Results:1.The results of T-MAZE: the latency of mid-dose and high-dose treatment groups were significantly increased(P<0.05)than those in the control group at the second,third,and fourth day;time spent in nutrition-rich chamber(EC)by high-dose treatment group was significantly decreased(P<0.05)than those in the control group at the second,third,and fourth day;time spent in nutrition-rich chamber(EC)by mid-dose treatment group was significantly decreased(P<0.05)than those in the control group at the third and fourth day.2.The results of brain tissue content of aluminium element: the brain tissue content of aluminium element of mid-dose and high-dose treatment groups were significantly increased(P<0.05)than those in the control group;the brain tissue content of aluminium element of high-dose treatment group was significantly increased(P<0.05)than that in the mid-dose treatment group.3.The results of ELISA: APP in mid-dose and high-dose treatment groups were significantly increased(P<0.05)than that in the control group;Aβ1-42 in high-dose treatment group was significantly increased(P<0.05)than that in the control group;Aβ1-40 in each group showed no statistically significant(P>0.05).4.The results of Real Time PCR: The gene’ expression of mTOR and AKT2 in mid-dose and high-dose treatment groups were significantly decreased(P<0.05)than those in low-dose treatment group and control group;The gene’ expression of AKT1,PI3 K in high-dose treatment groups were significantly decreased(P<0.05)than those in control group.the gene’ expression of appb,mapta in mid-dose and high-dose treatment groups were significantly increased(P<0.05)than those in the control group;the gene’ expression of appb in high-dose treatment group was significantly increased(P<0.05)than that in mid-dose treatment group;the gene’ expression of BDNF in mid-dose and high-dose treatment groups were significantly decreased(P<0.05)than those in low-dose treatment group and control group;the gene’ expression of BDNF in mid-dose treatment group was significantly decreased(P<0.05)than that in control group.The gene’ expression of RIP1,PARP2,Bmf1,jph3,rab25 and caspase8 in high-dose treatment group was significantly increased(P<0.05)than those in control group;The gene’ expression of PARP2、Bmf1 and rab25 in mid-dose treatment group was significantly increased(P<0.05)than those in control group;The gene’ expression of FADD and mag in each group showed no statistically significant(P>0.05).Conclusions:1.Zebrafish model of Alzheimer’s disease can be inducted by aluminium chloride successfully.2.The gene’ expression of RIP1,PARP2,Bmf1,jph3,rab25 and caspase8 induced by aluminum.3.The role of necroptosis in the Zebrafish model of Alzheimer’s disease induced by aluminum is important.