神经元性一氧化氮合酶活性在app/ps1双转基因AD模型小鼠皮质和海马的分布

本实验用 4～ 5月龄和 15～ 16月龄的 app/ ps1dtg小鼠各 5只 ,同龄野生型小鼠每个年龄组各 5只 ,用β-NADPH组织化学染色显示神经元一氧化氮合酶活性 ,刚果红组织学染色显示神经炎性斑 ,无偏性体视学计量皮质和海马神经炎斑的总体积 ,研究神经元一氧化氮合酶活性在 app/ ps1双转基因 (app/ ps1dtg) AD模型小鼠大脑皮质和海马的异常分布 ,探讨其在该模型小鼠及 AD患者脑内病理改变中的作用。结果显示 ,n NOS阳性神经元在各组小鼠皮质和海马内的分布没有区别 ,4～ 5月龄 app/ps1dtg小鼠皮质和海马可见神经炎斑 (NP)和营养不良性 NOS阳性神经突 (DTN) ;15～ 16月龄 app/ ps1dtg小鼠皮质和海马内NP的体积分别是 4～ 5月龄 app/ ps1dtg小鼠皮质 NP的 5倍 (P<0 .0 0 5 )和 8倍 (P<0 .0 0 1) ;15～ 16月龄 app/ ps1dtg小鼠皮质内 DTN的体积明显增大 (P<0 .0 1) ;且伴有 NOS阳性神经元形态的改变及海马 CA1 区 NOS阳性神经元数量的减少 (P<0 .0 5 ) ,DTN的形成与 NP呈正相关关系 (r=0 .85 ,P<0 .0 5 )。本实验结果表明 ,app/ ps1dtg小鼠能够模拟 AD患者脑内 NOS阳性神经元的病理改变 ,DTN的形成可能与 Aβ的毒性作用有关 ,DTN产生的 NO可能参与 app/ ps1dtg小鼠和 AD的神经病理过程。

ABERRANT DISTRIBUTION OF ACTIVITY OF NEURONAL NITRIC OXIDE SYNTHASE IN THE CORTEX AND HIPPOCAMPUS OF APP/PS1 DOUBLE TRANSGENIC MICE

App/ps1 double transgenic mice (app/ps1 dtg) aged at 4-5 and 15-16 months and the same age wild type mice were used in the present study. Each age group was 5 mice. β-NADPH histochemistry staining was used to show the activity of neuronal nitric oxide synthase(nNOS) and Congo red staining to show neuritic plaques (NP), and quantitative analysis for the total volume of the NP and dystrophy NOS positive neurite (DTN) in hippocampus and cortex by unbiased stereology method to study the aberrant distribution of the activity for nNOS in hippocampus and cortex of app/ps1 dtg mice, and to probe into the roles of nNOS/NO in AD and app/ps1 dtg mice. The results showed that there was no difference for the distribution of the nNOS positive neurons in cerebral cortex and hippocampus of each mice group; the NP and DTN could be seen in hippocampus and cortex of app/ps1 aged at 4-5 months. Compared to 4-5 months app/ps1 dtg mice, the total volume of NP in the cerebral cortex and hippocampus of 15-16 months app/ps1 dtg mice was increased 5 (P<0.005) and 8 folds (P<0.001) respectively, and the total volume of DTN in 15-16 months app/ps1 dtg mice was significance increased than 4-5 months app/ps1 dtg mice (P<0.01), and with morphological changes of NOS-positive neurons in cortex and nNOS-positive neuron loss in CA 1 region of hippocampus (P<0.05). Correlation analysis showed that positive relationship existed between the formation of DTN and Aβ deposition(r=0.85, P<0.05). The findings indicate the app/ps1 dtg mice can mimic the neuropathological changes for NOS positive neurons in AD, and the formation of DTN may relate to the toxicity of Aβ, and production of NO by DTN may be involved in the neuropathologic procedure in AD and app/ps1 dtg mice.