Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice.
Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice.
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DOI：
10.1186/1742-2094-8-112
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发表时间：
2011-09-07
影响因子：
9.3
通讯作者：
O'Banion MK
中科院分区：
文献类型：
--
作者：
Kyrkanides S;Tallents RH;Miller JN;Olschowka ME;Johnson R;Yang M;Olschowka JA;Brouxhon SM;O'Banion MK
本研究的目的是研究局部外周炎症，如骨关节炎，是否有助于体内神经炎症和神经退行性疾病。我们采用了诱导型Col 1-IL 1 βXAT小鼠骨关节炎模型，其中膝关节和颞下颌关节骨关节炎的诱导导致脑中星形胶质细胞和小胶质细胞活化，伴随炎症相关基因表达的上调。在阿尔茨海默病（AD）的APP/PS1小鼠模型中探索外周和脑炎症之间的联系的生物学意义，其中骨关节炎导致神经炎症以及AD病理的恶化和加速。在APP/PS1; Col 1-IL 1 βXAT复合转基因小鼠中，通过胶质细胞活化和炎症相关mRNA的定量评估，骨关节炎的诱导加剧并加速了神经炎症的发展，以及通过淀粉样斑块的数量和大小评估的Aβ病理学。这项工作支持了一个模型，通过该模型，外周炎症触发神经炎症的发展，随后诱导AD病理。更好地理解外周局部炎症（无论是骨关节炎、动脉粥样硬化还是其他疾病）与脑炎症之间的联系，可能对我们理解阿尔茨海默病、帕金森病和其他神经退行性疾病等疾病的病理生理学至关重要。
The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo. We employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology. Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse. This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases.
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影响因子：
15.1
作者：
Jaeger, Laura B.;Dohgu, Shinya;Sultana, Rukhsana;Lynch, Jessica L.;Owen, Joshua B.;Erickson, Michelle A.;Shah, Gul N.;Price, Tulin O.;Fleegal-Demotta, Melissa A.;Butterfiled, D. Allan;Banks, William A.
通讯作者：
Banks, William A.
影响因子：
5.3
作者：
Hickman, Suzanne E.;Allison, Elizabeth K.;El Khoury, Joseph
通讯作者：
El Khoury, Joseph
影响因子：
5.3
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
5.3
作者：
Kitazawa, M;Oddo, S;LaFerla, FM
通讯作者：
LaFerla, FM
影响因子：
5.3
作者：
Choi, Ji-Kyung;Jenkins, Bruce G.;Carreras, Isabel;Kaymakcalan, Sukru;Cormier, Kerry;Kowall, Neil W.;Dedeoglu, Alpaslan
通讯作者：
Dedeoglu, Alpaslan