Objective: To investigate the relations between neuroapoptosis and the onset and development of Alzheimer's disease (AD), especially the role of NF-kappaB in the regulation of neuroapoptosis.
Methods: Caspase-3 and NF-kappaB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods.
Results: Both neuronal apoptosis and NF-kappaB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF-kappaB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P < 0.01 or P < 0.05). Linear regression analyses of caspase-3 and NF-kappaB expression demonstrated a correlation between neuroapoptosis and activity of NF-kappaB.
Conclusion: The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-kappaB activity suggests a role of NF-kappaB in hippocampal neuroapoptosis.
目的: 探讨阿尔茨海默病(Alzheimer’s disease, AD)的发生、 发展与神经细胞凋亡之间的规律, 尤其是NF-κB在神经细胞凋亡中的调节作用。
方法: 以0–180日龄的Tg2576转基因小鼠作为研究对象, 正常野生型小鼠为对照, 应用caspase-3 和NF-κB 免疫组织化学、 免疫荧光双标、 Nissl 染色、 RT-PCR 等方法进行研究。 结果 随着小鼠日龄的增长, 对照组与模型组小鼠的海马CA3区锥体细胞中, 凋亡细胞密度和NF-κB阳性细胞密度逐渐下降; 出生14 d 以后, 模型组凋亡细胞密度和NF-κB阳性细胞密度均高于对照组(P < 0.05), 且小鼠海马caspase-3 mRNA表达水平与caspase-3 免疫组织化学结果基本吻合。 模型组NF-κB 和caspase-3 的表达水平均高于对照组。
结论: 凋亡相关基因NF-κB和caspase-3在AD的发病机制中可能起重要作用, NF-κB与神经细胞凋亡有正相关关系。 此外, caspase-3 与NF-κB 共同表达于同一细胞中, 提示NF-κB 的激活可能参与神经细胞凋亡的调节。