| Chronic IL-1β-Mediated Neuroinflammation Mitigates Amyloid Pathology in a Mouse Model of Alzheimer's Disease without Inducing Overt Neurodegeneration. | |
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MedLine Citation:
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PMID: 22173340 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 5 months of chronic neuroinflammation. Together, these observations point to a neuroprotective role for IL-1β in AD neuropathogenesis. |
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Authors:
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Sarah B Matousek; Simantini Ghosh; Solomon S Shaftel; Stephanos Kyrkanides; John A Olschowka; M Kerry O'Banion |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
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Title: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology Volume: - ISSN: 1557-1904 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Neurobiology & Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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