| Characterisation of amyloid-induced inflammatory responses in the rat retina. | |
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MedLine Citation:
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PMID: 21850448 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Amyloid-induced inflammation is thought to play a critical and early role in the pathophysiology of Alzheimer's disease. As such, robust models with relevant and accessible compartments that provide a means of assessing anti-inflammatory agents are essential for the development of therapeutic agents. In the present work, we have characterised the induction of inflammation in the rat retina following intravitreal administration of amyloid-beta protein (Aβ). Histology and mRNA endpoints in the retina demonstrate Aβ1-42-, but not Aβ42-1-, induced inflammatory responses characterised by increases in markers for microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1), GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines such as IL1-β, MIP1α and TNFα. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-β, MIP1α and MCP1, induced by Aβ1-42 but not Aβ42-1. This profile of pro-inflammatory gene and protein expression is consistent with that observed in the Alzheimer's disease brain and suggest that this preclinical model may provide a useful relevant tool in the development of anti-inflammatory approaches directed towards Alzheimer's disease therapy. |
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Authors:
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D R Howlett; S T Bate; S Collier; A Lawman; T Chapman; T Ashmeade; I Marshall; P J B Anderson; K L Philpott; J C Richardson; C J Hille |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-18 |
Journal Detail:
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Title: Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale Volume: - ISSN: 1432-1106 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0043312 Medline TA: Exp Brain Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK, david.howlett@kcl.ac.uk. |
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