Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice.
Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice.
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小胶质细胞激活与增强的肿瘤坏死因子-Alpha和单核细胞化学吸收剂蛋白-1表达的早期相关性在三重转基因阿尔茨海默氏病小鼠的内嗅皮层中特异性。
DOI：
10.1186/1742-2094-2-23
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发表时间：
2005-10-18
影响因子：
9.3
通讯作者：
Bowers, William J.
中科院分区：
文献类型：
--
作者：
Janelsins, Michelle C.;Mastrangelo, Michael A.;Oddo, Salvatore;LaFerla, Frank M.;Federoff, Howard J.;Bowers, William J.
阿尔茨海默病是一种复杂的神经退行性疾病，其病理特征为β-淀粉样蛋白（Aβ）沉积、神经元缠结形成和突触变性的时间和空间进展。炎症过程涉及在脑内引发和/或传播AD相关病理，因为炎性细胞因子表达和其他炎症标志物在患有AD病理的个体中明显。当前的研究检查了3xTg-AD小鼠模型中炎症过程是否在疾病过程的早期明显，以及炎症特征是否存在地区差异。冠状脑切片用于鉴定2、3和6个月3xTg-AD和非转基因对照小鼠中的Aβ。对2、3和6个月的3xTg-AD和非转基因小鼠的显微解剖的内嗅皮层和海马组织进行定量实时RT-PCR。在含有3xTg-AD和非转基因内嗅皮质和海马的切片中使用无偏体视学定量小胶质细胞/巨噬细胞数量。我们在3个月时在3xTg-AD小鼠中观察到人Aβ沉积，该沉积在6个月时增强。有趣的是，我们在3xTg-AD小鼠的内嗅皮质中观察到TNF-α上调14.8倍，MCP-1上调10.8倍，但在海马或非转基因小鼠的任何区域中均未检测到随时间的变化。此外，这种增加与3xTg-AD内嗅皮质中F4/80阳性小胶质细胞和巨噬细胞的特异性增加相关。我们的数据为淀粉样蛋白和神经纤维缠结病理模型中炎症过程的早期诱导提供了证据。此外，我们的研究结果将内嗅皮层内的炎症过程联系起来，内嗅皮层是最早受AD影响的大脑区域之一。
Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ) deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.
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影响因子：
5.3
作者：
Afagh, A;Cummings, BJ;Tenner, AJ
通讯作者：
Tenner, AJ
影响因子：
7
作者：
Braak, H;Braak, E
通讯作者：
Braak, E
影响因子：
158.5
作者：
in 't Veld, BA;Ruitenberg, A;Stricker, BHC
通讯作者：
Stricker, BHC
影响因子：
--
作者：
Haroutunian, V;Perl, DP;Mohs, RC
通讯作者：
Mohs, RC
DOI：
10.1073/pnas.96.6.3228
发表时间：
1999-03-16
影响因子：
11.1
作者：
Hsia, AY;Masliah, E;Mucke, L
通讯作者：
Mucke, L