大鼠海马内注射β淀粉样蛋白促进神经细胞增殖

Proliferation of Neurons Caused by Intrahippocampal Injection of Aggregated β-amyloid in Rat

目的观察脑内β淀粉样蛋白(β-amyloid,AB)沉积对神经细胞增殖的影响。方法将Aβ_(1-42)定位注射至大鼠双侧海马,对照组注射反序列Aβ_(42-1)或PBS。腹腔注射Brdu标记增殖细胞。用免疫组化和免疫荧光检测溴脱氧尿苷(Bromodeoxyuridine,Brdu)标记细胞和doublecortin(DCX)阳性细胞。结果海马内注射Aβ_(1- 42)后引起海马齿状回颗粒下层(subgranular zone,SGZ)和侧脑室下层(subventricular zone,SVZ)Brdu标记细胞及DCX阳性细胞显著增加(P<0.01)。双免疫荧光分析表明许多Brdu标记细胞表达DCX。结论Aβ沉积可以促进脑内的神经细胞增殖,提示这种现象可能为阿尔茨海默病的一种代偿性应答。促进神经细胞增殖的措施对于治疗阿尔茨海默病具有重要的价值。

Objective To investigate the effect of β -amyloid （A β ） deposits on neuron proliferation. Methods Aggregated A β1-42 was stereotaxicaly injected into the hippocampus of rats and reverse peptide A β 1-42 or phosphate buffer saline （PBS） were injected as controls. Proliferating cells were labeled with intraperitoneal injection of Bromodeoxyuridine （BrdU）. Brain sections were analyzed with immunohistochemistry and immunofluorescence to determine Brdu labelled newborn cells and doublecortin （DCX） labelled immature neurons. Results Aβ1-42significantly increased the number of BrdU labelled cells and the expression of DCX in two neuroproliferative regions-the subgranular zone of the dentate gyrus and the rostral subventricular zone（P〈0.01）. Most cells labelled with BrdU expressed the immature neuronal markers DCX, suggesting that they were nascent neurons. Conclusion Proliferation cells in Aβ deposited models suggest that neurogenesis may be a compensatory response and the method could have therapeutic potential for Alzheimer＇s disease （AD）.