Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis
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BioMed Central
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Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis Yuemang Yao1, Cinzia Chinnici1, Hanguan Tang1, John Q Trojanowski2,3, Virginia MY Lee2,3 and Domenico Praticò*1 Address: 1Center for Experimental Therapeutics and Department of Pharmacology; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA, 2Center for Neurodegenerative Disease Research; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA and 3Institute on Aging; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA Email: Yuemang Yao - [email protected]; Cinzia Chinnici - [email protected]; Hanguan Tang - [email protected]; John Q Trojanowski - [email protected]; Virginia MY Lee - [email protected]; Domenico Praticò* - [email protected] * Corresponding author
Published: 22 October 2004 Journal of Neuroinflammation 2004, 1:21
doi:10.1186/1742-2094-1-21
Received: 22 September 2004 Accepted: 22 October 2004
This article is available from: http://www.jneuroinflammation.com/content/1/1/21 © 2004 Yao et al; licensee BioMed Central Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: An increasing body of evidence implicates both brain inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance of their interaction in vivo, however, is unknown. Previously, we have shown that separate pharmacological targeting of these two components results in amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD-like brain amyloidosis (Tg2576). Methods: In the present study, we investigated the therapeutic effects of a combination of an antiinflammatory agent, indomethacin, and a natural anti-oxidant, vitamin E, in the Tg2576 mice. For this reason, animals were treated continuously from 8 (prior to Aβ deposition) through 15 (when Aβ deposits are abundant) months of age. Results: At the end of the study, these therapeutic interventions suppressed brain inflammatory and oxidative stress responses in the mice. This effect was accompanied by significant reductions of soluble and insoluble Aβ1-40 and Aβ1-42 in neocortex and hippocampus, wherein the burden of Aβ deposits also was significantly decreased. Conclusions: The results of the present study support the concept that brain oxidative stress and inflammation coexist in this animal model of AD-like brain amyloidosis, but they represent two distinct therapeutic targets in the disease pathogenesis. We propose that a combination of antiinflammatory and anti-oxidant drugs may be a useful strategy for treating AD.
Introduction Alzheimer's disease (AD) is the most common, complex and challenging form of neurodegenerative disease associated with dem
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