The Effects Of Human Umbilical Cord Mesenchymal Stem Cells Treatment On The Cerebral Aβ Pathway In PPswe/PSEN1 Transgenic Mice

Objective: To explore the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)therapy about the formation of Aβ in APPswe/PSNE1 double transgenic mice.Method: Use hUC-MSCs to inject 12 months APPswe/PSEN1 double transgenic mice,equal amounts of PBS inject the control groups.After inject 2,4,6 times in every group,use Morris water maze constant temperature swimming pool to detect the changes of behavioristics,use RT-PCR methods to detect APP/BACE1 m RNA level,use Western blotting methods to detect each group BACE1/APP/PS1/GFAP/NF-kB protein levels,use immunohistochemical methods to observe Aβ/Nestin/Dcx distribution in the brain.Result: After inject 2,4,6 times,the escape lentency is hUC-MSCs group<control group(T=2.419,P<0.05;T=2.448,P<0.05;T=3.048,P<0.01),and the BACE1 mRNA expression levels is hUC-MSCs group<control group(T=14.951,P < 0.01;T=21.035,P < 0.01;T=24.736,P < 0.01),the APP mRNA expression levels is hUC-MSCs group<control group(T=31.066,P<0.01;T=34.818,P<0.01;T=48.050,P < 0.01),After inject 2,4,6 times,the protein expression level of BACE1 is hUC-MSCs group<control group(T=85.066,P<0.01;T=73.936,P<0.01;T=80.857,P<0.01);After inject 2,4,6 times,the protein expression level of APP is hUC-MSCs group<control group(T=19.355,P<0.01;T=19.525,P<0.01;T=29.710,P<0.01);After inject 2,4,6 times,the protein expression level of PS1 is hUC-MSCs group<control group(T=15.953,P<0.01;T=30.815,P<0.01;T=46.170,P<0.01);After inject 2,4,6 times,the protein expression level of NF-kB is hUC-MSCs group<control group(T=33.965,P<0.01;T=33.359,P<0.01;T=8.112,P<0.01);After inject 2,4,6 times,the protein expression level of GFAP is hUC-MSCs group<control group(T=62.612,P<0.01;T=70.268,P<0.01;T=43.374,P<0.01);Aβ distribution in the brain hUC-MSCs group<control group(cortex: T=10.059,P<0.001;T=16.859,P<0.001;T=7.778,P<0.001,hippocampus: T=25.108,P<0.001;T=40.758,P<0.001;T=15.249,P<0.001);After inject 6 times,the level of Dcx and Nestin is hUC-MSCs group>control in dentate gyrus of the hippocampus of AD mice.Conclusion: hUC-MSCs can improve spatial memory ability of AD mice.hUC-MSCs can reduce the deposition of Aβ,may through effecting the process of transcription and translation about BACE1/APP in mice brain,decreasing the activity and expression of BACE1/PS1.hUC-MSCs can lessen the expression of GFAP and NF-kB,reducing the associated inflammatory response.hUC-MSCs can promote neurogenesis in dentate gyrus of the hippocampus of AD mice.