Abstract |
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 | 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 |
Journal | Experimental brain research
(Exp Brain Res)
Vol. 214
Issue 2
Pg. 185-97
(Oct 2011)
ISSN: 1432-1106 [Electronic] Germany |
PMID | 21850448
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Amyloid
- Amyloid beta-Peptides
- Biomarkers
- Chemokines
- Cytokines
- Peptide Fragments
- amyloid beta-protein (1-42)
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Topics |
- Amyloid
(administration & dosage, toxicity)
- Amyloid beta-Peptides
(administration & dosage, toxicity)
- Animals
- Astrocytes
(metabolism, pathology)
- Biomarkers
(metabolism)
- Chemokines
(biosynthesis)
- Cytokines
(biosynthesis)
- Female
- Humans
- Inflammation
(etiology, metabolism, pathology)
- Intravitreal Injections
- Microglia
(metabolism, pathology)
- Peptide Fragments
(administration & dosage, toxicity)
- Rats
- Retina
(metabolism, pathology)
- Retinitis
(etiology, pathology)
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