Chronic IL-1β-mediated neuroinflammation mitigates amyloid pathology in a mouse model of Alzheimer's disease without inducing overt neurodegeneration.
Chronic IL-1β-mediated neuroinflammation mitigates amyloid pathology in a mouse model of Alzheimer's disease without inducing overt neurodegeneration.
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DOI：
10.1007/s11481-011-9331-2
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发表时间：
2012-03
影响因子：
6.2
通讯作者：
O'Banion, M. Kerry
中科院分区：
文献类型：
--
作者：
Matousek, Sarah B.;Ghosh, Simantini;Shaftel, Solomon S.;Kyrkanides, Stephanos;Olschowka, John A.;O'Banion, M. Kerry
神经炎症是中枢神经系统（CNS）中对有害刺激的局部组织反应，其特征在于神经胶质反应性、细胞因子和趋化因子的诱导以及血管通透性。细胞因子白细胞介素（IL）-1β在CNS损伤后迅速诱导，并且在神经退行性疾病如阿尔茨海默病（AD）中长期表达。我们最近开发了一种在脑中持续产生IL-1β的新方法，以研究IL-1β与AD发病机制之间的联系。利用这个模型，我们以前已经证明了斑块大小和频率的减少伴随着强大的神经炎症反应。这些观察结果仅限于AD斑块沉积过程中的单个早期时间点，未研究其他神经退行性终点。为了将这些观察结果扩展到疾病进展的其他阶段并评估其他病理标志物，我们研究了年龄和IL-1β过表达持续时间对同源C57 BL/6背景的APPswe/PS-1dE 9 AD模型的影响。我们现在报道，IL 1 β过度表达导致6 E10免疫阳性斑块病理学减少，与年龄或持续时间无关。我们还研究了在该AD模型的背景下，IL-1β过表达是否导致神经元凋亡或胆碱能轴突变性。虽然我们可以证明浸润性炎性细胞的凋亡，我们没有发现IL-1相关的神经元凋亡或胆碱能轴突变性的证据，即使在慢性神经炎症5个月后。总之，这些观察结果表明IL-1β在AD神经发病机制中具有神经保护作用。
Neuroinflammation is a local tissue response to injurious stimuli in the central nervous system (CNS) and is characterized by glial reactivity, induction of cytokines and chemokines, and vascular permeability. The cytokine interleukin (IL)-1β is rapidly induced following CNS insult, and is chronically expressed in neurodegenerative disorders such as Alzheimer’s disease (AD). We recently developed a novel method of sustained IL-1β production in the brain to study the link between IL-1β and AD pathogenesis. Utilizing this model, we have previously demonstrated reduction of plaque size and frequency accompanied by a robust neuroinflammatory response. These observations were limited to a single early time point in the course of AD plaque deposition and did not investigate other neurodegenerative endpoints. To extend these observations to other stages of disease progression and evaluate additional pathologic markers, we investigated the effects of age and duration of IL-1β overexpression in the APPswe/PS-1dE9 AD model on a congenic C57BL/6 background. We now report that IL1β overexpression leads to decreased 6E10 immunopositive plaque pathology regardless of age or duration. We also investigated whether IL-1β overexpression led to neuronal apoptosis or cholinergic axonal degeneration in the context of this AD model. Although we could demonstrate apoptosis of infiltrating inflammatory cells, we found no evidence for IL-1 associated apoptosis of neurons or cholinergic axon degeneration even after five months of chronic neuroinflammation. Together, these observations point to a neuroprotective role for IL-1β in AD neuropathogenesis.
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影响因子：
9.3
作者：
Giunta B;Fernandez F;Nikolic WV;Obregon D;Rrapo E;Town T;Tan J
通讯作者：
Tan J
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
影响因子：
4.7
作者：
Matousek, Sarah B.;Hein, Amy M.;O'Banion, M. Kerry
通讯作者：
O'Banion, M. Kerry
影响因子：
3.3
作者：
GEULA, C;MESULAM, MM
通讯作者：
MESULAM, MM
影响因子：
15.1
作者：
Hein, Amy M.;Stasko, Melissa R.;Matousek, Sarah B.;Scott-McKean, Jonah J.;Maier, Steven F.;Olschowka, John A.;Costa, Alberto C. S.;O'Banion, M. Kerry
通讯作者：
O'Banion, M. Kerry