阿尔茨海默病病理 APPswe/PS1dE9 小鼠模型中细胞因子、胆碱能标志物和淀粉样β沉积的表达谱分析。
Expression Profiling of Cytokine, Cholinergic Markers, and Amyloid-β Deposition in the APPSWE/PS1dE9 Mouse Model of Alzheimer's Disease Pathology.
机构信息
Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
Department of Physiology, Divisions of Chemistry and Biochemistry, Pharmacology and Neuroscience, City University of New York Medical School, New York, NY, USA.
出版信息
J Alzheimers Dis. 2018;62(1):467-476. doi: 10.3233/JAD-170999.
BACKGROUND
Alzheimer's disease (AD), a neurodegenerative disease, is associated with dysfunction of the olfactory and the entorhinal cortex of the brain that control memory and cognitive functions and other daily activities. Pro-inflammatory cytokines, amyloid-β (Aβ), and the cholinergic system play vital roles in the pathophysiology of AD. However, the role of changes in cholinergic system components, Aβ accumulation, and cytokines in both the olfactory and entorhinal cortex is not known clearly.
OBJECTIVE
The present study is aimed to evaluate the changes of cholinergic system components, Aβ accumulation, and cytokines in both the olfactory bulb (OB) and entorhinal cortex (EC) of young and aged APPSWE/PS1dE9 transgenic (Tg) mice.
METHODS
We have explored the changes of cholinergic system components, Aβ accumulation, and expression profiling of cytokines in the OB and EC of aged APPswe transgenic mice and age-matched wild type mice using quantitative Real-Time PCR assays and immunohistochemistry techniques.
RESULTS
In aged Tg mice, a significant increase of expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and chemokine MCP1 (p < 0.001, p < 0.001, and p = 0.001, respectively) and a significant reduction of nAChRα4 (p = 0.048) and AChE (p = 0.023) was observed when compared with age-matched wild type mice. Higher levels of AChE and BuChE are expressed in OB and EC of the APPSWE/PS1dE9 of Tg mice. Aβ accumulation was observed in OB and EC of the APPSWE/PS1dE9 of Tg mice.
CONCLUSION
The study demonstrates the expression profiling of pro-inflammatory cytokines and cholinergic markers as well as Aβ accumulation in OB and EC of the APPSWE/PS1dE9 Tg mice. Moreover, the study also demonstrated that the APPSWE/PS1dE9 Tg mice can be useful as a mouse model to understand the role of pro-inflammatory cytokines and cholinergic markers in pathophysiology of AD.
背景
阿尔茨海默病（AD）是一种神经退行性疾病，与大脑嗅觉和内嗅皮层的功能障碍有关，这些区域控制着记忆、认知功能和其他日常活动。促炎细胞因子、淀粉样蛋白-β（Aβ）和胆碱能系统在 AD 的病理生理学中起着至关重要的作用。然而，尚不清楚胆碱能系统成分、Aβ 积累和细胞因子在嗅球（OB）和内嗅皮层（EC）中的变化。
目的
本研究旨在评估年轻和老年 APPswe/PS1dE9 转基因（Tg）小鼠嗅球（OB）和内嗅皮层（EC）中胆碱能系统成分、Aβ 积累和细胞因子表达谱的变化。
方法
我们使用定量实时 PCR 检测和免疫组织化学技术，探索了老年 APPswe 转基因小鼠和同龄野生型小鼠 OB 和 EC 中胆碱能系统成分、Aβ 积累和细胞因子表达谱的变化。
结果
在老年 Tg 小鼠中，与同龄野生型小鼠相比，白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和趋化因子 MCP1 的表达显著增加（p<0.001、p<0.001 和 p=0.001），nAChRα4（p=0.048）和乙酰胆碱酯酶（AChE）（p=0.023）的表达显著降低。APPSWE/PS1dE9 Tg 小鼠的 OB 和 EC 中 AChE 和 BuChE 的表达水平较高。APPSWE/PS1dE9 Tg 小鼠的 OB 和 EC 中观察到 Aβ 积累。
结论
本研究表明，APPSWE/PS1dE9 Tg 小鼠的 OB 和 EC 中促炎细胞因子和胆碱能标志物以及 Aβ 积累的表达谱。此外，本研究还表明，APPSWE/PS1dE9 Tg 小鼠可作为一种有用的小鼠模型，以了解促炎细胞因子和胆碱能标志物在 AD 病理生理学中的作用。
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