三重转基因阿尔茨海默病动物模型的神经再生研究

Study of Neurogenesis in Triple-Transgenic Alzheimer Disease Mice Model

目的探讨不同鼠龄 APP/PS1/Tau 三重转基因阿尔茨海默病小鼠(3xTg-AD)室管膜下层(Subventricular zone,SVZ)及海马齿状回(dentate gyrus,DG)神经细胞增殖变化及与β淀粉样斑块的关系。方法采用3月龄和12月龄 A PP/PS1/Tau 三重转基因小鼠(3xTg-AD)作为实验组,同龄同种系野生型小鼠作为对照组,BrdU 标记增殖细胞。Doublecortin(DCX),BrdU 免疫荧光双标染色未成熟神经细胞,计数室管膜下层和海马齿状回 BrdU 阳性细胞数和 DCX/BrdU 双标阳性细胞数。免疫组化法检测β淀粉样斑块。结果 12月龄组3xTg-AD 小鼠与对照组野生型小鼠相比,室管膜下区及海马齿状回 BrdU 阳性细胞明显减少(P<0.05),3月龄组无明显差异(P>0.05)。3月龄组3xTg-AD 小鼠未见β淀粉样斑块形成,12月龄组3xTg-AD 小鼠有明显的β淀粉样斑块形成。结论 12月龄3xTg-AD 小鼠室管膜下层及海马齿状回脑内神经再生能力明显下降,与β淀粉样斑块形成可能相关。

Objective To investigate the proliferation of different age 3xTg Alzheimer disease(AD)mice in dentate gyrus(DG)and subventricle zone(SVZ)as well as the relationship between beta amyloid plaque accumula- tion and neurogenesis.Methods Three and twelve months old 3xTgAD male mice were used for the experiment group,and the age-matched wild type male animal models for the control group.These animal studies were performed using bromodeoxyurine(BrdU)labeling the newly generated cell,DCX & BrdU double labeled cells as the immature neural cells,counting both BrdU(+)and BrdU/DCX(+)cells,using immunohistochemistry to identify beta amy- loid plaques.Results The number of Brdu(+)and BrdU/DCX(+)cell counts in12-month-old 3xTgAD mice was less than that of its wild type littermates.Brdu(+)and BrdU/DCX(+)cell counts were not different in 3- month-old mice.β-Amyloid immunohistochemistry showed amyloid deposition in 1-year-old but not in 3-month-old 3xTgAD mice.Conclusion The proliferation in DG and SVZ was decreased in 12-month-old 3xTgAD mice,and neurogenesis declines,which may be connected with amyloid-β senile plaque formation.