Aβ_(25-35)抑制成年小鼠海马齿状回区神经前体细胞增殖  

Aβ_(25-35 )inhibits the proliferation of neural precursor cells in the dentate gyrus of adult mouse

作　　者：李学坤[1] 左萍萍[1] 孔令娜[1] 张卿[1] 

机构地区：[1]中国医学科学院基础医学研究所.中国协和医科大学基础医学院药理学系,北京100005

出　　处：《中国药理学通报》2004年第7期808-811,共4页Chinese Pharmacological Bulletin

摘　　要：目的　观察Aβ2 5-3 5对成年小鼠海马神经前体细胞增殖的影响。方法　 2 0只成年BALB/c小鼠随机分为对照组和模型组 ,对照组注射等量无菌生理盐水 ,模型组侧脑室注射 3μlAβ2 5-3 5(1g·L-1)。动物分别在Aβ2 5-3 5注射后d 5、10、2 0、30灌流处死。动物每次处死前均腹腔注射 3次BrdU(5 0mg·kg-1,间隔 8h)。鼠脑切取冰冻切片 ,进行神经元特异性核蛋白 (NeuN)免疫荧光和BrdU免疫组织化学染色 ,以观察神经元数目及其前体细胞增殖情况。结果　对照组小鼠海马神经细胞形态清晰完整 ,排列规则 ,而侧脑室注射Aβ2 5-3 5后的小鼠海马NeuN阳性细胞数明显减少 ,且同部位的BrdU阳性细胞数目亦明显减少 (P <0 .0 1)。结论　Aβ2 5-3 5在中枢神经系统不仅表现为对成熟神经元的毒性作用 ,而且还明显抑制神经前体细胞的增殖 ,从而影响神经的发生过程。Aim To explore the effect of Amyloid-beta (25～35) peptide (Aβ 25-35) on the proliferation of neural precursor cells in the dentate gyrus of adult BALB/c mouse. Methods Adult mice were randomly divided into control group and model group(Aβ 25-35Ⅰ, Aβ 25-35Ⅱ, Aβ 25-35Ⅲ, Aβ 25-35Ⅳ). 3 μl aggregated Aβ 25-35 (1 g·L -1) was intraventricularly injected into the lateral ventricle. Before each perfusion, BrdU (50 mg·kg -1×3, interval 8 h) was injected ip to label the neural precursor cells. Animals were transcardially perfused with 4% paraformaldehyde in PBS respectively at 5,10,20,30 days after the Aβ 25-35 injection. Mouse brain was removed and serially sectioned on a freezing-sliding microtome at 40 μm. NeuN immunofluorescence and BrdU immunohistology were processed. Results It was found that Aβ 25-35 not only injured the mature neurons and decreased the number of NeuN positive neurons, but also significantly decreases the number of BrdU positive cells and inhibited the proliferation of neural precursor cells. Conclusion Aβ 25-35 could inhibit the proliferation of neural precursor cells in the dentate gyrus of adult mouse. It indicates that its toxicity is involved in the inhibition of neurogenesis in vivo.

关 键 词：β淀粉样蛋白25~35片段 海马齿状回 神经前体细胞 细胞增殖 小鼠 

分 类 号：R-332[医药卫生] R322.81